
apobec3jii

apobec 3jii (apolypoprotein bii marnah editting ensime, kaattalitik subunit 3jii) proteinukalude apobec suuppar faamiliyil ulppedunna apobec 3jii jeane encode cheytha oru manushya ensaimaanu. proteinukalude eee kudumbam swathasidhamaaya aanti vairal prathirodhasheshiyil oru pradhana punk vahikkumennu nirddeshikkappettittund. otappetta dna substratil cytidine euridinilekku demination cheiyunnathinu uthejippikkunna cytidine deeminesukalude kudumbatthil pedunna onnaanu apobec 3jii. eiii3jiyude sii-terminal domaine kaattalitik pravartthanam nalkunnu, niravadhi enmr, kristtal gadanakal substrate savisheshathayum kaattalitik pravartthanavum vishadeekarikkunnu.
sariyaaya replicationil edapedunnathiloode retrovirusukalkkethire, prathyekichu echuaivikkethire apobec 3jii swathasidhamaaya aanti retroviral rogaprathirodha pravartthanam nadathunnu. ennirunnaalum, echuaivi polulla lentivirusukal eee phalathe prathirodhikkunnathinaayi vairal infectivity factor (iif) protein vikasippicheduthittundu. iif apobec 3jiyumaayi samvadikkukayum protesomaliloode apobec 3jiyude sarvavyaapithvathinum apachayathinum kaaranamaakukayum cheiyunnu. maruvashathu, phoomi virusukal apobec 3jiyude cytoplasmic layikkunnathine thadassappeduthunna oru aaksasari protein bettu () uthpaadippikkunnu. prathirodhatthinte rund vazhikalum parasparam vyathyasthamaan, pakshe avaykku parasparam "inn vivo" aayi maattisthaapikkaan kazhiyum.
kandethal.
jarmus mattullavarum chernnaanu ithu aadyamaayi thiricharinjathu."2002ll chromosome 22ll apobec3eiii muthal 3jii vareyulla proteinukalude kudumbatthile amgamenna nilayilum pinneedu vairal aaksasari protein wife illaatha echuaivi-1nte pakarpp niyantrikkaan kazhiyunna oru sellular gadakamenna nilayilum. taamasiyaathe, cytidine deminase apobec 1-maayi homology kaaranam orumichu grooppucheytha proteinukalude oru kudumbatthil pettayaalaan apobec 3 jii ennu kaanichu.
ghadana.
apobec3jick oru samamiti gadanayundu, athinte falamaayi 2 homologous kaattalitik domainukal, enn-terminal (sidi 1), sii-terminal (sidi 2) domainukal, oronninum oru ekopana saitt adangiyirikkunnu. oro domainilum cytidine deeminesukalkkaayi addehathinte/cys-x-glu-x 23-28-proo-sais-x2-sais rooparekhayundu. ennirunnaalum, saadhaarana cytidine deminaseukalil ninnu vyathyasthamayi, kaattalatik domainile rund beetta sheettukalkkidayil oru cofactor binding saitaakaan kazhiyunna oru savishesha alfa helix apobec 3jiyil adangiyirikkunnu. (chithram 1)
sidi2 kaattalittikkaayi sajeeva demination motif specificiatic pradhaanavumaanu. sidi1 kaattalittikkaayi nishkriyamaanu, pakshe dnauma rnaumaayum bandhippikkunnathin valare pradhaanamaan, koodaathe apobec 3jii deminationte 5 '-> 3' prosessivity nirvachikkunnathil ithu pradhaanamaan. sidi1-nte saannidhyamillaathe sidi2-nuu deminase pravartthanamilla.
monomerukal, dimerukal, trimerukal, tetramerukal, uyarnna oordar oligomarukal enniva chernnathaanu native apobec 3jii. apobec3jii oru dimeraayi pravarthikkunnuvennu karuthappedunnundengilum, ithu yadhaarthathil monomerukaludeyum oligomarukaludeyum mishrithamaayi pravartthikkaan saadhyathayund.
sidi1 (chithram 1)-ll sthithicheyyunna dii128 amino assid avashishtangal, ifumaayulla apobec 3jii edapedalukalkku prathyekichum pradhaanamaanennu thonnunnu, kaaranam oru dii128qaaeeii pooyint mutation apobec 3jiyude iif-ashrita ksheenam thadayunnu. koodaathe, apobec 3jiyile amino aasidukal 128-130 negatteevu charjju cheytha oru rooparekha undaakkunnu, ithu ifumaayulla edapedalukalkkum apobec 3jii-iif complexukalude roopeekaranathinum nirnaayakamaan. koodaathe, apobec 3jii echuaivi-1 vairanukalaayi ulppeduthunnathinum thathfalamaayundaakunna aanti retroviral pravartthanatthinum avashishtangal 124-127 pradhaanamaan.
pravartthana samvidaanam.
apobec 3jii vyaapakamaayi padikkukayum echuaivi-1 replicatione prathikoolamaayi badhikkunna niravadhi samvidaanangal kandethukayum cheythittundu.
cytidine demination hypermutation.
apobec3jick ore kudumbatthile mattu proteinukalkkum aaktiveshan-induced (cytidine) deminaseukalaayi (sahayam) pravartthikkaan kazhiyum. echuaivi dnaude negatteevu strandle niravadhi deoxitedine muthal deoxuridine mutationukal vare prerippichukondu apobec 3jii reverse transcriptionil edapedunnu, praadhamikamaayi 3 '-> 5' prosess reethiyil complimentary dna (cdna) aayi prakadippikkunnu. apobec 3jii apobec suuppar faamiliyude bhagamaayathinaal oru sahayiyaayi pravarthikkunnathinaal, cytidine deminationaayi apobec 3jii madhyasthatha vahikkunna samvidaanam oru iii-ykku samaanamaayirikkaam. apobec 1-nuu valare samaroopamaanennu ariyappedunna koolii cytidine deminase nucleotide, sink-binding mekhalaykku chuttum sahayikkunnu. sink-coordinated ensime cytidine pyrimidine valayathinte sthaanam 4-ll nerittu nucleophilic akramanam nadathunnathiloodeyaanu pravachikkapetta demination prathikaranam nayikkappedunnathu. prottoon, hydroxyl group daathaakkalude uravidamaayi vellam aavasyamaanu (chithram 2). sthaanam 4-leeii demination (thathfalamaayundaakunna ooksideshan) oru carbonyl group nalkukayum sittidinil ninnu euridinilekku maarukayum cheiyunnu.
demination pravartthanam aathyanthikamayi proviral dnaude "hoott spottukalil" jii → oru hyper mutationukalkku kaaranamaakunnu. atharam hypermutation aathyanthikamayi vairasinte coding replicative seshiyum nasippikkukayum athinte falamaayi pravarthanarahithamaaya niravadhi vairanukal undaakukayum cheiyunnu. proteinu retroviral dna parivartthanam cheyyaan kazhiyaathavidham athinte sajeeva saitt parivartthanam cheyyumbol apobec 3jick valare durbalamaaya aantivairal prabhavam undu. apobec3jii-mediated demination parivartthana avashishtangalilekku aakarshikkappedunna dna repire sisttangal vazhi vairal dna degradationilekku parokshamaayi nayikkumennu aadyam karuthiyirunnu. ennirunnaalum, manushyante apobec 3jii dna repire ensaimukalaaya ung, smug 1 ennivayil ninnu swathanthramaayi vairal cdna alavu kuraykkunnu ennathinaal ithu kizhivu nalkiyittundu.
reverse traanscriptionile edapedal.
dna deminationil ninnu swathanthramaayi echuaivi-1-nte reverse transcriptionil apobec 3jii edapedunnu. reverse transcription aarambhikkunnathin trana3lies saadhaaranayaayi echuaivi-1 primer binding saittumaayi bandhippikkunnu. apobec 3jick traina 3lies primingine thadayaan kazhiyum, athuvazhi vairal ssdna ulppaadanatheyum vairas anubadhayeyum prathikoolamaayi badhikkunnu. vairal rnaumaayi bandhippikkukayum sterik maattangalkk kaaranamaakukayum cheiyunna apobec 3jii reverse transcriptione prathikoolamaayi baadhikkumenn pravachikkappedunnu.
vairal dna samyojanathil edapedal.
pravarthanaparamaaya kaattalatik domainukaleyum deminase pravartthanatheyum aashrayich hoost genome vairal dna samyojanathinte edapedalumaayi apobec 3jii bandhappettirikkunnu. emm. bii. aii. esum mattullavarum. dna mainus strandle ninnu primer trana prosess cheiyunnathilum neekkam cheiyunnathilum apobec 3jii edapedunnuvennu kandu, angane ithu asaadhaaranamaaya vairal 3 'neelamulla terminal repeat (ltr) dna avasaanikkunnu. eee vairal dna attangal samyojanathinum plus-strand dna kaimaattatthinum kaaryakshamamallatha substrateukalaanu. thalphalamaayi, echuaivi-1 provirus roopeekaranam thadayunnu.
jaivaparamaaya pravartthanam.
echuaivi encapsidation.
anuvadaneeyamallaatha koshangal ennu vilikkappedunna chila koshangalil apobec 3 jii mrna prakadippikkunnu, athil iiefinte abhaavathil echuaivi-1 nuu shariyaayi badhikkaanum aavarthikkaanum kazhiyilla. atharam koshangalil shaareerikamaayi prasakthamaaya praadhamika sidi4tii lymphocytukalum macrophageukalum ulppedunnu. apobec 3jii echuaivi-1 vairiyanukalilekku ulppeduthunnathu apobec 3jii vyapanathinum aanti-retroviral pravartthanatthinte parishramatthinum valare pradhaanamaan. nirddishta naalu samvidaanangalenkilum (chithram 3) apobec 3jii yude encapsidation sambhavikkaam 1. apobec 3jii 2-nte nirddishtamallaatha packaging. hoost rna 3-yumayullah apobec 3jii edapedal. vairal rna 4-yumayullah apobec 3jii edapedal. echuaivi-1 gagg proteinukalumaayulla apobec 3jii edapedal. avasaanathe rund samvidaanangalkku maathrame vipulamaaya pinthuna labhichittulloo. 
virionukalil ulppeduthunna alavu vairiyon uthppaadippikkunna koshatthinullile apobec 3 jii eksprashante nilavaaratthe aasrayichirikkunnu. xu thudangiyava. pbmc koshangalumayi padanangal nadathukayum, vaifinte abhaavathil, 7 ± 4 apobec 3 jii thanmathrakal virionukalil samyojippikkappedukayum echuaivi-1 replication sakthamaaya reethiyil thadayukayum cheythathayi kandethukayum cheythu.
exogenous retrovirusukalude pakarcha thadayunnathinupurame, eiii3jii manushya endogenous retrovirusukalilum pravartthikkunnu, avayil hyper mutationukalude samanamaaya signecharukal avasheshikkunnu.
rogathinte prasakthi.
anuvadaneeyamallaatha kosangalkkullil prakadippikkunna apobec 3 jii echuaivi-1 replicationteyum anubaadhayudeyum pradhana prathirodha gadakamaanu. ennirunnaalum, iif eee aanti retroviral gadakathe prathirodhikkukayum apobec 3jii pravartthanatthinte saannidhyathil praayogikavum anubaadhayundaakkunnathumaya echuaivi-1 vairanukalude uthpaadanam praapthamaakkukayum cheiyunnu. prathyekichum, iif echuaivi-1 virionukalil apobec 3jii ulppeduthunnathu thadayukayum matellaa echuaivi-1 proteinukalil ninnum swathanthramaaya reethiyil ensaiminte naashathe prolsaahippikkukayum cheiyunnu.
echuaivi-1ll sakthamaaya aantivairal efakttukal prakadippikkunna oru supradhana proteinaayi apobec 3jii saadhaaranayaayi padikkappettittundile, sameepakaala padanangal echuaivi-1 nte vyaapanam sugamamakkaan sahaayikkunnathin apobec 3jii-mediated myootteshante saadhyatha vyakthamaakkiyittund. mungananayulla pradeshangalile deminationukalude ennam onnu muthal palathilekku vyathyaasappedunnu, ithu apobec 3jii exposure cheiyunna samayathe ashrayichirikkum. koodaathe, intra sellular apobec 3 jii saandrathayum vairal hypermutationte alavum thammil oru doses prathikaranamundennu theliyikkappettittund. apobec 3jii-niyantritha provirus praayogikamaaya provirus thammilulla punasamyojanam sambhavichu ennathukondo apobec 3jii-niyantritha provirusukal valare kurachu mutationukal vahikkunnathukondo apobec 3jii-madhyastha mutationulla chila echuaivi-1 provirusukal abhivridhi praapikkunnathayi theliyikkappettittund. atharam sablethal mutagenesis echuaivi-1 vairas janasamkhyayil kooduthal janithaka vaividhyathin sambhavana cheiyunnu, ithu echuaivi-1-nte poruthappedaanum pracharippikkanum ulla kazhivu vardhippikkunnathinulla apobec 3jii-yude saadhyatha prakadamaakkunnu.

