identification of conserved protein domains that span a wide range of biological functions provide deep insights regarding the origin and evolution of complex biological systems , these versatile conserved domains often have catalytic or structural roles that can be utilized , with small variations , in different contexts . the p - loop - containing nucleotide phosphatase fold represents one such catalytic domain that is utilized in almost every conceivable biological system in all the three superkingdoms of life . folds such as the sh3-like barrels , the pas - like fold , the ob fold , the double - stranded -helix , the -propeller and rubredoxin - like zinc ribbons are predominantly non - catalytic domains that are widely represented in multiple functional contexts , with roles such as small - molecule binding , nucleic - acid binding and interaction with other proteins   ( see also the scop   and cath   databases ) . versatile globular domains appear to have emerged fairly early in evolution in various fold classes , such as the / or + mixed folds , or the all- and all- folds . comparative genomics and evolutionary studies indicate that many of these versatile folds probably emerged in contexts related to rna binding in the ancient translation system and were subsequently re - utilized in other biological systems . of particular interest in this context are the small all- folds that assume conformations such as barrels or -helices . these structures have considerable potential for functional versatility , because they are able either to accommodate small molecules within cavities formed by the curved -sheets or to interact with various larger molecules , especially nucleic acids or proteins , via the external surfaces of the sheets . a few ancient and widespread -rich folds such as the sh3-like barrel and the ob fold appear to have colonized multiple functional niches early in evolution , although their earliest versions may have had roles related to rna metabolism . we were interested in identifying other such functionally versatile -rich folds that could be traced back to the early stages of life 's evolution . the availability of extensive genome sequence data and advances in structure determination over recent years allow the successful application of comparative genomics , sequence and structure comparisons to identify any such folds that may be somewhat less widely represented than the ob or sh3-like folds . here , we identify one such -barrel fold typified by the globular domain of the h subunit of the photosynthetic reaction center ( prc - h ) from purple proteobacteria such as rhodopseudomonas viridis . the purple bacterial photosynthetic reaction center consists of three primary subunits , of which prc - l and prc - m primarily bind the pigments involved in photochemistry , whereas prc - h appears to be a key regulator of electron transfer between the quinones in photosynthetic reaction centers . so far , homologs of the h subunit have only been found in photosynthetic proteobacteria   and the carboxy - terminal globular domain of prc - h shows a distinct -barrel fold that is structurally unrelated to other characterized -barrels . here we use sequence - profile analysis and comparative genomics to show that the -barrel domain of prc - h defines a novel , widespread superfamily of -barrel domains that is represented in several bacterial , plant and archaeal genomes . we also show that this -barrel domain is found in the conserved protein rimm , which is involved in rna processing and ribosomal assembly in the course of translation . thus we provide evidence for an unexpected evolutionary connection between rna metabolism , translation and the redox reactions in photosynthesis in the form of a shared functionally versatile -barrel domain . the prc - h subunit is a membrane - spanning protein with a single amino - terminal transmembrane helix . its crystal structure reveals a cytoplasmic region comprising a largely non - globular segment followed by a -barrel - like structure . the entire cytoplasmic region has been classified as a novel -rich fold with no relatives in the scop database . however , we observed that the most carboxy - terminal part of the cytoplasmic region forms a distinct folding unit in the form of a six - stranded -barrel that could define a novel evolutionarily conserved domain ( figure 1 ) . a dali search   of the pdb database with this -barrel revealed no specific structural relationships with other folds such as the ob fold or the sh3-like barrel beyond the presence of curved -sheets , suggesting that it represents a domain with a distinct fold ( figure 2 ) . to further investigate its evolutionary relationships , we used the sequence of this -barrel unit from the prc - h protein ( gi : 132177 , residues 151 - 257 ) of rhodopseudomonas viridis in a psi - blast   search of the non - redundant ( nr ) database at the national center for biotechnology information ( ncbi ) . this search ( expect value ( e ) threshold for inclusion in profile = 0.01 ) recovered , in addition to the orthologs of the prc - h proteins from other purple proteobacteria , several uncharacterized proteins from the cyanobacterium anabaena ( for example , all5315 and alr5332 , iteration 2 , e = 10 - 10 ) , non - photosynthetic -proteobacteria such as mesorhizobium , sinorhizobium , brucella and caulobacter ( for example , smc00885 , iteration 4 , e = 10 or cac1676 , iteration 5 , e = 10 ) , several other assorted bacteria like deinococcus , bacillus and streptomyces ( for example , ylmc iteration 4 , e = 10 ) and several archaea with completely sequenced genomes . interestingly , in addition to these proteins , this search also recovered the ribosome - associated rimm protein from bacteria ( for example , rimm , deinococcus radiodurans , iteration 6 , e = 10 ) . to establish the validity of these relationships we collected all the true positives detected in this search and clustered them on the basis of similarity , obtained diverse representatives belonging to each cluster , and seeded psi - blast searches with each of them . the majority of these searches recovered approximately the same set of proteins with statistically significant e - values . for example a search started with the archaeal protein ta0943 ( gi : 10640258 , whole length ) recovers rimm ( from vibrio cholerae , iteration 4 , e = 10 ) , and the prc - h protein ( r. viridis , iteration 8 , e = 10 ) . although some of these searches converged prematurely , they consistently recovered true positives detected in the other searches with at least borderline statistical significance ( e approximately 0.05 - 0.01 ) . we prepared separate multiple sequence alignments of this region for all the major , distinct clusters of the proteins detected in the above searches and predicted secondary structure for each of them . the predicted secondary structure   corresponded perfectly with that of the barrel domain of the classic prc - h proteins . furthermore , the smallest proteins with this region were detected in the euryarchaea ( for example , ta0943 ) and their length of approximately 80 residues exactly corresponded to that of the -barrel that forms a distinct folding unit seen in the prc - h subunit . consistent with this , several proteins , such as mll3685 from mesorhizobium loti , have duplications or triplications of this region , which indicate that the boundaries of each repeat correspond perfectly to the -barrel unit of prc - h . these observations suggest that this region indeed defines a novel evolutionarily mobile domain of approximately 80 residues ( figure 3 ) . we named it the prc - barrel after the photosynthetic reaction center subunit h , in which it was first observed . most of the sequence conservation in the prc - barrel is centered on the hydrophobic residues that stabilize the six strands of the domain . additionally , there is a nearly invariant glycine ( figure 3 ) that corresponds to the beginning of strand 2 and is likely to stabilize the first -hairpin in the structure . beyond the conserved core , there is considerable variability in the residues in the loops , and these are likely to impart the specificity required for the diverse interactions of this superfamily . the experimentally characterized prc - barrel - containing proteins possess diverse biological functions : the prc - h subunits themselves are involved in photosynthesis in the purple bacteria , whereas rimm is a protein that associates with the 30s ribosomal subunit and is required for efficient translation and processing of 16s rna . gene - disruption studies in rhodobacter capsulatus indicate that loss of the prc - h subunit results in disruption of the reaction center and the light - harvesting complex-1 and loss of photosynthetic growth . biochemical studies have pointed out that the prc - barrel of the purple bacterial prc - h lies on the cytosolic face of the reaction center and directly affects the redox processes during the photosynthetic reaction . on photoactivation there is an electron - transfer chain from the primary donor - the bacteriochlorophyll molecules - to the primary quinone , and then to the secondary quinone . a glutamate residue ( e173 in r. viridis prc - h ) located in the loop between strand 2 and 3 of the prc domain is in the vicinity of the secondary quinone of the reaction center . the site - directed mutagenesis of this glutamate severely retards the first and second electron transfers from the primary quinone that successively reduce the secondary quinone to semi - quinone and quinol . the crystal structure of the reaction center reveals that this acidic residue of the prc - barrel is situated close to other acidic residues from the prc - l subunit , which interact with the quinone . thus , the acidic residue in the loop between the prc could act as a regulator of the electrostatic state of the reaction complex to potentiate electron transfer . the multiple alignment ( figure 3 ) of the prc - barrel reveals that this glutamate , or an equivalent acidic residue , is conserved in the majority of prc - barrels that are most closely related to the prc - h version . in addition to the purple bacteria , such versions are seen in the cyanobacteria , -proteobacteria such as rhizobia , agrobacterium tumefaciens and brucella melitensis , and deinococcus radiodurans ( figure 3 ) . in the case of the cyanobacteria , it is possible that some of the prc - h - like proteins that contain an equivalent acidic residue might associate with their very distinct photosynthetic reaction centers , by analogy with their purple bacterial counterparts . one of these proteins from anabaena cylindrica is exclusively expressed in the spore - like akinetes , though its actual function remains unknown . the extensive spread of this version of the domain in non - photosynthetic proteobacteria such as the rhizobia , suggest that a similar mechanism of regulating electron transfers may , perhaps , be used in regulating non - photosynthetic electron - transfer reactions . many prc - barrels , including those of the rimm family , lack the acidic residue typical of those related to the prc - h subunit and required for redox regulation . the crystal structure shows that the prc - barrel domain mediates a contact with the amino - terminal cytoplasmic peptide of the prc - m subunit and also makes contacts with the other structurally less ordered regions of the prc - h polypeptide   ( figure 1 ) . this suggests that , in addition to the specific electrostatic regulatory function , the prc - barrel mediates specific interactions with other molecules through multiple surfaces . these interactions are consistent with the ' foundational role ' postulated for the prc - h protein in the assembly of the reaction center . such a protein - protein interaction role in the assembly of complexes could be a potential function of the prc - barrels that do not possess the features suggestive of redox regulation . given that rimm specifically associates with the 30s ribosomal subunit rather than the fully assembled ribosome , and participates in the maturation of the 16s rrna , it is possible that the carboxy - terminal prc - barrel could be used to bind rna or proteins . an acidic residue at the beginning of strand 3 and a patch of large and acidic residues at the extreme amino terminus of the prc - barrel that is specific to the rimm proteins are of particular interest in this regard ( figure 3 ) . on the basis of the structure of the prc - barrel it can be predicted that in rimm these residues are likely to line a cleft that may accommodate a peptide from an interacting protein ( figures 1,3 ) . other surfaces of the prc - barrel in the rimm protein could interact with other proteins , or , alternatively , interact with rna . the original report on the crystal structure of the photosynthetic reaction center suggested that the region corresponding to the prc - barrel of the prc - h subunit could bind a small - molecule ligand . while the structure of the prc - barrels with a central aperture ( figures 1,2 ) makes this a tempting possibility , currently there is no evidence to support the possibility that these domains bind small - molecule ligands . the phyletic patterns and relationships of the prc - barrels have a number of important implications , including some for the evolution of the photosynthetic reaction center in bacteria . phylogenetic analysis and similarity - based clustering show that these domains essentially form three large and distinct groups ( figure 4 ) and at least two smaller clusters . the prc - h subunits and their close relatives from cyanobacteria , non - photosynthetic -proteobacteria and d. radiodurans form the first of these groups . in addition , they are also seen in multiple copies in the cyanobacterium anabaena , the actinomycete streptomyces coelicolor , d. radiodurans and the euryarchaeon methanosarcina acetivorans . in this group , the prc - barrel occurs either linked to amino - terminal transmembrane helices or as tandem repeats , with up to three copies , or linked to another -helical repetitive domain also found in the bacillus protein ysnf ( figure 4 ) . most members of this group contain a negatively charged residue in the loop between strand 2 and 3 ( figure 3 ) that could be implicated in electrostatic regulatory processes , as in the case of prc - h proper . the second major group is represented in all the euryarchaeal genomes available to date and is additionally found in a few gram - positive bacteria . all proteins belonging to this class are the stand - alone minimal version of the prc - barrel . these are the most prevalent of all the prc - barrel proteins and are present in a single copy in all bacterial proteomes available to date , and also in plants in the form of a chloroplast - derived version . the rimm proteins have an additional specific amino - terminal -strand - rich domain with no detectable relationship to other domains . in addition to these three major groups , there is one small group that has representatives only in the cyanobacteria and plants ( figures 2,4 ) and appears to contain more distant relatives of the prc - h - like prc - barrels . all members of this group contain two copies of the prc - barrel , and , in most cases , one of these copies contains an acidic residue in the loop between strand 2 and 3 that might be equivalent to the classic prc - h - like regulatory acidic residue . the presence of a predicted amino - terminal transit peptide in the plant proteins suggests that it probably functions in the chloroplast , and that these proteins may , in part , have a regulatory function analogous to the prc subunit . the other small group , typified by the bacillus subtilis protein yrrd , has so far been found only in the actinomycetes , gram - positive bacteria and d. radiodurans ( figures 3,4 ) . this group is most closely related to the above - discussed plant - cyanobacterial group , and is ultimately a distant relative of the larger prc - h like group . most members of this group have duplicate copies of the prc - barrel domain and typically lack the acidic residue in the loop between strands 2 and 3 . the phyletic pattern of rimm is reminiscent of proteins that for part of the ribosome or participate in rna metabolism . likewise , the presence of the euryarchaeal - type solo prc - barrels in every euryarchaeal genome , despite the metabolic diversity of these euryarchaea , suggests that these proteins probably have a core cellular function . one likely possibility is that they function in rna metabolism , perhaps as the archaeal equivalents of rimm . in contrast to these two groups of prc - barrels , the prc - h - like group and their more distant relatives have a phyletic distribution , mainly limited to bacteria or archaea with large genomes and complex metabolism . this suggests that they were , perhaps , derived later in bacteria evolution from a version involved in rna metabolism . the extensive presence of multiple copies of the prc - h - like versions in diverse -proteobacteria suggests that this particular form , with the characteristic acidic residue , was derived in their common ancestor . a corollary to this is that these proteins probably functioned , initially , as regulators of electron - transfer chains in non - photosynthetic energy metabolism systems in the ancestral -proteobacterium . they were subsequently utilized in the photosynthetic reaction center after a subset of these bacteria acquired photosynthesis . the phylogenetic tree supports a close relationship between some of the cyanobacterial prc - barrels and the prc - h proteins of the photosynthetic -proteobacteria ( figure 4 ) . this implies that the cyanobacteria probably acquired these forms of the prc - barrel through lateral transfer from the purple bacteria and may have incorporated them as regulatory subunits into the organizationally distinct cyanobacterial photosystems   or into other uncharacterized electron - transfer chains . this is consistent with the previously observed case of horizontal transfer of -proteobacterial reaction - center genes , including that for prc - h , into the -proteobacteria . the prc - h subunit is a membrane - spanning protein with a single amino - terminal transmembrane helix . its crystal structure reveals a cytoplasmic region comprising a largely non - globular segment followed by a -barrel - like structure . the entire cytoplasmic region has been classified as a novel -rich fold with no relatives in the scop database . however , we observed that the most carboxy - terminal part of the cytoplasmic region forms a distinct folding unit in the form of a six - stranded -barrel that could define a novel evolutionarily conserved domain ( figure 1 ) . a dali search   of the pdb database with this -barrel revealed no specific structural relationships with other folds such as the ob fold or the sh3-like barrel beyond the presence of curved -sheets , suggesting that it represents a domain with a distinct fold ( figure 2 ) . to further investigate its evolutionary relationships , we used the sequence of this -barrel unit from the prc - h protein ( gi : 132177 , residues 151 - 257 ) of rhodopseudomonas viridis in a psi - blast   search of the non - redundant ( nr ) database at the national center for biotechnology information ( ncbi ) . this search ( expect value ( e ) threshold for inclusion in profile = 0.01 ) recovered , in addition to the orthologs of the prc - h proteins from other purple proteobacteria , several uncharacterized proteins from the cyanobacterium anabaena ( for example , all5315 and alr5332 , iteration 2 , e = 10 - 10 ) , non - photosynthetic -proteobacteria such as mesorhizobium , sinorhizobium , brucella and caulobacter ( for example , smc00885 , iteration 4 , e = 10 or cac1676 , iteration 5 , e = 10 ) , several other assorted bacteria like deinococcus , bacillus and streptomyces ( for example , ylmc iteration 4 , e = 10 ) and several archaea with completely sequenced genomes . interestingly , in addition to these proteins , this search also recovered the ribosome - associated rimm protein from bacteria ( for example , rimm , deinococcus radiodurans , iteration 6 , e = 10 ) . to establish the validity of these relationships we collected all the true positives detected in this search and clustered them on the basis of similarity , obtained diverse representatives belonging to each cluster , and seeded psi - blast searches with each of them . the majority of these searches recovered approximately the same set of proteins with statistically significant e - values . for example a search started with the archaeal protein ta0943 ( gi : 10640258 , whole length ) recovers rimm ( from vibrio cholerae , iteration 4 , e = 10 ) , and the prc - h protein ( r. viridis , iteration 8 , e = 10 ) . although some of these searches converged prematurely , they consistently recovered true positives detected in the other searches with at least borderline statistical significance ( e approximately 0.05 - 0.01 ) . we prepared separate multiple sequence alignments of this region for all the major , distinct clusters of the proteins detected in the above searches and predicted secondary structure for each of them . the predicted secondary structure   corresponded perfectly with that of the barrel domain of the classic prc - h proteins . furthermore , the smallest proteins with this region were detected in the euryarchaea ( for example , ta0943 ) and their length of approximately 80 residues exactly corresponded to that of the -barrel that forms a distinct folding unit seen in the prc - h subunit . consistent with this , several proteins , such as mll3685 from mesorhizobium loti , have duplications or triplications of this region , which indicate that the boundaries of each repeat correspond perfectly to the -barrel unit of prc - h . these observations suggest that this region indeed defines a novel evolutionarily mobile domain of approximately 80 residues ( figure 3 ) . we named it the prc - barrel after the photosynthetic reaction center subunit h , in which it was first observed . most of the sequence conservation in the prc - barrel is centered on the hydrophobic residues that stabilize the six strands of the domain . additionally , there is a nearly invariant glycine ( figure 3 ) that corresponds to the beginning of strand 2 and is likely to stabilize the first -hairpin in the structure . beyond the conserved core , there is considerable variability in the residues in the loops , and these are likely to impart the specificity required for the diverse interactions of this superfamily . the experimentally characterized prc - barrel - containing proteins possess diverse biological functions : the prc - h subunits themselves are involved in photosynthesis in the purple bacteria , whereas rimm is a protein that associates with the 30s ribosomal subunit and is required for efficient translation and processing of 16s rna . gene - disruption studies in rhodobacter capsulatus indicate that loss of the prc - h subunit results in disruption of the reaction center and the light - harvesting complex-1 and loss of photosynthetic growth . biochemical studies have pointed out that the prc - barrel of the purple bacterial prc - h lies on the cytosolic face of the reaction center and directly affects the redox processes during the photosynthetic reaction . on photoactivation there is an electron - transfer chain from the primary donor - the bacteriochlorophyll molecules - to the primary quinone , and then to the secondary quinone . a glutamate residue ( e173 in r. viridis prc - h ) located in the loop between strand 2 and 3 of the prc domain is in the vicinity of the secondary quinone of the reaction center . the site - directed mutagenesis of this glutamate severely retards the first and second electron transfers from the primary quinone that successively reduce the secondary quinone to semi - quinone and quinol . the crystal structure of the reaction center reveals that this acidic residue of the prc - barrel is situated close to other acidic residues from the prc - l subunit , which interact with the quinone . thus , the acidic residue in the loop between the prc could act as a regulator of the electrostatic state of the reaction complex to potentiate electron transfer . the multiple alignment ( figure 3 ) of the prc - barrel reveals that this glutamate , or an equivalent acidic residue , is conserved in the majority of prc - barrels that are most closely related to the prc - h version . in addition to the purple bacteria , such versions are seen in the cyanobacteria , -proteobacteria such as rhizobia , agrobacterium tumefaciens and brucella melitensis , and deinococcus radiodurans ( figure 3 ) . in the case of the cyanobacteria , it is possible that some of the prc - h - like proteins that contain an equivalent acidic residue might associate with their very distinct photosynthetic reaction centers , by analogy with their purple bacterial counterparts . one of these proteins from anabaena cylindrica is exclusively expressed in the spore - like akinetes , though its actual function remains unknown . the extensive spread of this version of the domain in non - photosynthetic proteobacteria such as the rhizobia , suggest that a similar mechanism of regulating electron transfers may , perhaps , be used in regulating non - photosynthetic electron - transfer reactions . many prc - barrels , including those of the rimm family , lack the acidic residue typical of those related to the prc - h subunit and required for redox regulation . the crystal structure shows that the prc - barrel domain mediates a contact with the amino - terminal cytoplasmic peptide of the prc - m subunit and also makes contacts with the other structurally less ordered regions of the prc - h polypeptide   ( figure 1 ) . this suggests that , in addition to the specific electrostatic regulatory function , the prc - barrel mediates specific interactions with other molecules through multiple surfaces . these interactions are consistent with the ' foundational role ' postulated for the prc - h protein in the assembly of the reaction center . such a protein - protein interaction role in the assembly of complexes could be a potential function of the prc - barrels that do not possess the features suggestive of redox regulation . given that rimm specifically associates with the 30s ribosomal subunit rather than the fully assembled ribosome , and participates in the maturation of the 16s rrna , it is possible that the carboxy - terminal prc - barrel could be used to bind rna or proteins . an acidic residue at the beginning of strand 3 and a patch of large and acidic residues at the extreme amino terminus of the prc - barrel that is specific to the rimm proteins are of particular interest in this regard ( figure 3 ) . on the basis of the structure of the prc - barrel it can be predicted that in rimm these residues are likely to line a cleft that may accommodate a peptide from an interacting protein ( figures 1,3 ) . other surfaces of the prc - barrel in the rimm protein could interact with other proteins , or , alternatively , interact with rna . the original report on the crystal structure of the photosynthetic reaction center suggested that the region corresponding to the prc - barrel of the prc - h subunit could bind a small - molecule ligand . while the structure of the prc - barrels with a central aperture ( figures 1,2 ) makes this a tempting possibility , currently there is no evidence to support the possibility that these domains bind small - molecule ligands . the phyletic patterns and relationships of the prc - barrels have a number of important implications , including some for the evolution of the photosynthetic reaction center in bacteria . phylogenetic analysis and similarity - based clustering show that these domains essentially form three large and distinct groups ( figure 4 ) and at least two smaller clusters . the prc - h subunits and their close relatives from cyanobacteria , non - photosynthetic -proteobacteria and d. radiodurans form the first of these groups . they are represented in multiple copies in the proteomes of most -proteobacteria . in addition , they are also seen in multiple copies in the cyanobacterium anabaena , the actinomycete streptomyces coelicolor , d. radiodurans and the euryarchaeon methanosarcina acetivorans . in this group , the prc - barrel occurs either linked to amino - terminal transmembrane helices or as tandem repeats , with up to three copies , or linked to another -helical repetitive domain also found in the bacillus protein ysnf ( figure 4 ) . most members of this group contain a negatively charged residue in the loop between strand 2 and 3 ( figure 3 ) that could be implicated in electrostatic regulatory processes , as in the case of prc - h proper . the second major group is represented in all the euryarchaeal genomes available to date and is additionally found in a few gram - positive bacteria . all proteins belonging to this class are the stand - alone minimal version of the prc - barrel . these are the most prevalent of all the prc - barrel proteins and are present in a single copy in all bacterial proteomes available to date , and also in plants in the form of a chloroplast - derived version . the rimm proteins have an additional specific amino - terminal -strand - rich domain with no detectable relationship to other domains . in addition to these three major groups , there is one small group that has representatives only in the cyanobacteria and plants ( figures 2,4 ) and appears to contain more distant relatives of the prc - h - like prc - barrels . all members of this group contain two copies of the prc - barrel , and , in most cases , one of these copies contains an acidic residue in the loop between strand 2 and 3 that might be equivalent to the classic prc - h - like regulatory acidic residue . the presence of a predicted amino - terminal transit peptide in the plant proteins suggests that it probably functions in the chloroplast , and that these proteins may , in part , have a regulatory function analogous to the prc subunit . the other small group , typified by the bacillus subtilis protein yrrd , has so far been found only in the actinomycetes , gram - positive bacteria and d. radiodurans ( figures 3,4 ) . this group is most closely related to the above - discussed plant - cyanobacterial group , and is ultimately a distant relative of the larger prc - h like group . most members of this group have duplicate copies of the prc - barrel domain and typically lack the acidic residue in the loop between strands 2 and 3 . the phyletic pattern of rimm is reminiscent of proteins that for part of the ribosome or participate in rna metabolism . likewise , the presence of the euryarchaeal - type solo prc - barrels in every euryarchaeal genome , despite the metabolic diversity of these euryarchaea , suggests that these proteins probably have a core cellular function . one likely possibility is that they function in rna metabolism , perhaps as the archaeal equivalents of rimm . in contrast to these two groups of prc - barrels , the prc - h - like group and their more distant relatives have a phyletic distribution , mainly limited to bacteria or archaea with large genomes and complex metabolism . this suggests that they were , perhaps , derived later in bacteria evolution from a version involved in rna metabolism . the extensive presence of multiple copies of the prc - h - like versions in diverse -proteobacteria suggests that this particular form , with the characteristic acidic residue , was derived in their common ancestor . a corollary to this is that these proteins probably functioned , initially , as regulators of electron - transfer chains in non - photosynthetic energy metabolism systems in the ancestral -proteobacterium . they were subsequently utilized in the photosynthetic reaction center after a subset of these bacteria acquired photosynthesis . the phylogenetic tree supports a close relationship between some of the cyanobacterial prc - barrels and the prc - h proteins of the photosynthetic -proteobacteria ( figure 4 ) . this implies that the cyanobacteria probably acquired these forms of the prc - barrel through lateral transfer from the purple bacteria and may have incorporated them as regulatory subunits into the organizationally distinct cyanobacterial photosystems   or into other uncharacterized electron - transfer chains . this is consistent with the previously observed case of horizontal transfer of -proteobacterial reaction - center genes , including that for prc - h , into the -proteobacteria . we show that the carboxy - terminal -barrel domain of the h subunit of the photosynthetic reaction center defines a novel all--sheet fold , representatives of which are widespread throughout the prokaryotic world . homologs of prc - h , with a conserved acidic residue that has been shown to have a role in regulating electron transfer in the reduction of the secondary quinone of reaction centers , are also found in non - photosynthetic  -proteobacteria , cyanobacteria , d. radiodurans and the archaeon m. acetivorans . it appears likely that the prc - h - like version of the prc - barrels was first derived in the ancestral -proteobacteria , followed by dissemination into other lineages . probably , these proteins originally functioned in non - photosynthetic electron - transfer chains and were subsequently incorporated into the photosynthetic apparatus after its emergence in the -proteobacteria . in addition , this domain also appears to mediate specific protein - protein interactions . this is likely to be the principal role of versions of this domain present in the pan - bacterial rimm proteins and other proteins widely distributed in bacteria and archaea . a protein comprising only a stand - alone copy of the prc - barrel is conserved in all the euryarchaeal proteomes available to date , and , by analogy with the rimm protein , is predicted to function in rna metabolism . it seems possible that prc - barrels with a sporadic distribution and a regulatory function in energy metabolism or photosynthesis are likely to have been derived from more conserved and ancient versions that were probably involved in rna metabolism . the identification of this domain may help in the exploration of hitherto unexplored facets of diverse biological processes such as photosynthesis , energy metabolism and rna metabolism . the non - redundant ( nr ) database of protein sequences at ncbi was searched using the blastp program . profile searches were conducted using the psi - blast program with either a single sequence or an alignment used as the query , with a profile - inclusion expectation ( e ) value threshold of e = 0.01 , and were iterated until convergence . before use in psi - blast searches , no such bias that could skew the statistics of sequence relationships in searches of the nr database was detected . accordingly , to achieve maximum sensitivity , all searches were run with the compositional - bias - based statistics turned off . multiple alignments were constructed using the t_coffee program , followed by manual correction based on the psi - blast results . structural manipulations were carried out using the swiss - pdb viewer program   and the ribbon diagrams were constructed with molscript . protein secondary structure was predicted using a multiple alignment as the input for the program phd . signal peptides were predicted using signalp   and the transmembrane regions were predicted using topred . phylogenetic analysis was carried out using the maximum - likelihood , neighbor - joining and least squares methods . briefly , this involved the construction of a least - squares tree using the fitch program or a neighbor - joining tree using the neighbor program ( both from the phylip package ) , followed by local rearrangement using the protml program of the molphy package   to arrive at the maximum likelihood ( ml ) tree . the statistical significance of various nodes of this ml tree was assessed using the relative estimate of logarithmic likelihood bootstrap ( protml rell - bp ) with 10,000 replicates . a ribbon representation of the h ( gold ) and the m ( gray ) subunits of the photosynthetic reaction complex ( pdb 1 eys ) . the two acidic residues projecting in the direction of the membrane , including the glutamate ( e ) involved in regulation of quinone reduction , are shown in space - filling representation . the peptide from the amino - terminal tail of the m subunit that interacts with a cleft in the prc - barrel ( pcr - m peptide ) is also shown in space - filling representation . a comparison of the prc - barrel with the analogous -barrels , namely the sh3-like barrel and the ob fold . ( a ) the representative of the sh3-like barrel is the dihydrofolate reductase subunit ( pdb 1vie ) and ( b ) the representative of the ob fold is the cold - shock protein s1-like rna - binding domain ( pdb 1mjc ) . note the difference in packing of the last strand of the ob fold with respect to the first strand in the sh3-like barrel and ( c ) the prc - barrel . in the case of the ob fold , note the difference in orientation of the second strand with respect to the first as compared to the other two -barrels . a multiple alignment of the prc - barrel was constructed using t - coffee   and realigning the sequences by parsing high - scoring pairs from psi - blast search results . the secondary structure assigned by phd   is shown above the alignment , with e representing a -strand , and h an -helix . the 85% consensus shown below the alignment was derived using the following amino - acid classes : hydrophobic ( h , alicvmyfw , yellow shading ) ; the aliphatic subset of the hydrophobic class ( l , alivmc , yellow shading ) ; small ( s , acdgnpstv , green ) and polar ( p , cdehknqrst , blue ) . a ' g ' denotes the conserved g of the tiny subset of the small class . columns of residues that are peculiar to a particular category of prc - barrels ( see text ) are colored red . the numbers within the alignment are non - conserved inserts that have not been shown . the sequences are denoted by their gene name followed by the species abbreviation and genbank identifier ( gi ) . the species abbreviations are : archaea : af , archaeoglobus fulgidus ; hsp , halobacterium sp . nrc-1 ; mac , methanosarcina acetivorans ; mta , methanobacterium thermoautotrophicum ; mj , methanococcus jannaschii ; ph , pyrococcus horikoshii ; tac , thermoplasma acidophilum ; bacteria : atu , agrobacterium tumefaciens ; aae , aquifex aeolicus ; ana , anabaena sp . ; bs , bacillus subtilis ; bb , borrelia burgdorferi ; bmel , brucella melitensis ; cac , clostridium acetobutylicum ; ccr , caulobacter crescentus ; cj , campylobacter jejuni ; des , desulfitobacterium hafniense ; drad , deinococcus radiodurans ; ec , escherichia coli ; hi , haemophilus influenzae ; hp , helicobacter pylori ; mlo , mesorhizobium loti ; mtu , mycobacterium tuberculosis ; nm , neisseria meningitidis ; pae , pseudomonas aeruginosa ; pmar , prochlorococcus marinus ; rcap , rhodobacter capsulatus ; rp , rickettsia prowazekii ; rsp , rhodobacter sphaeroides ; rvi , rhodopseudomonas viridis ; sli , streptomyces lividans ; sme , sinorhizobium meliloti ; scoe , streptomyces coelicolor a3 ; syco , synechococcus sp . ; ssp , synechocystis sp . ; tm , thermotoga maritima ; tp , treponema pallidum ; ter , trichodesmium erythraeum ; tsyn , thermosynechococcus elongatus ; ttep , thermochromatium tepidum ; xf , xylella fastidiosa ; plants : at , arabidopsis thaliana . phylogenetic relationships of the prc - barrel - containing proteins along with the domain architectures . the phyletic pattern of each family is shown , along with the number of proteins ( if there is more than one ) . the thickness of a given branch is approximately proportional to the number of proteins contained within it . ysnf , a repeat domain typified by the bacillus subtilis ysnf protein ; n - term , the specific amino - terminal domain of the rimm proteins .
the prc - h -barrel domain , a distinct cytoplasmic -barrel domain whose fold has no close structural relationship to any other well known -barrel domain , is the prototype of a novel superfamily of protein domains approximately 80 residues long . 
 this domian is a widespread , ancient domain that appears to have been recruited to a variety of biological systems , ranging from rna processing to photosynthesis .