9.8: Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The unfolded or partially folded polypeptides, which are often intermediates in the folding pathway, are stabilized by chaperones, leading to the final correctly folded state. Without chaperones, the unfolded or partially folded polypeptides may misfold or form insoluble aggregates. This is particularly observed in proteins in which the carboxy or C-terminus is required for the correct folding of the amino or N-terminus. In such cases, a chaperone can bind and stabilize the N-terminal part of the polypeptide in an unfolded conformation until the rest of the peptide chain is synthesized and the whole protein can fold correctly.
Chaperones can also stabilize unfolded polypeptide chains as they are transported into subcellular organelles. For instance, during the transfer of proteins into the mitochondria from the cytosol, it is easier for partially unfolded conformations to be transported across the mitochondrial membrane. During the transport, the partially unfolded polypeptides are stabilized by chaperones.
Additionally, chaperones play an important role in the assembly of proteins that have a complex structure, such as multi-subunit proteins. These proteins comprise multiple polypeptide chains - each of which needs to be correctly folded and then assembled in a specific manner. In the processes involved, chaperones assist in protein folding and the stabilization of unassociated components while other parts of the protein are undergoing assembly.
Chaperones ya Molekuli na Folding ya Protini: Utaratibu wa asili wa protini huundwa na mwingiliano kati ya minyororo ya upande wa asidi za amino zinazounda. Asidi za amino hazina uwezo wa kuungana, hivyo protini haiwezi kujipinda yenyewe na inahitaji kuandamana. Chaperones hazisambazi habari yoyote ya ziada inayohitajika kwa folding ya polypeptides; muundo wa asili wa protini huamuliwa tu na mfululizo wake wa asidi ya amino. Chaperones catalyze protini folding bila kuwa sehemu ya protini folded. Polypeptides unfolded au sehemu folded, ambayo ni mara nyingi kati katika njia ya folding, ni stabilized na chaperones, na kusababisha mwisho kwa usahihi folded hali. Bila chaperones, unfolded au sehemu folded polypeptides inaweza misfold au kuunda aggregates insoluble. Hii ni hasa kuonekana katika protini ambayo carboxy au C-mwisho inahitajika kwa folding sahihi ya amino au N-mwisho. Katika kesi kama hizo, chaperone inaweza kuunganisha na kuimarisha sehemu ya N-terminal ya polypeptide katika muundo uliofunikwa hadi sehemu iliyobaki ya mlolongo wa peptidi itakapotengenezwa na protini nzima inaweza kukunjwa kwa usahihi. Chaperones pia inaweza kuimarisha unfolded polypeptide minyororo kama wao ni kusafirishwa katika organelles subcellular. Kwa mfano, wakati wa uhamisho wa protini katika mitochondria kutoka cytosol, ni rahisi kwa conformations sehemu unfolded kusafirishwa katika utando mitochondrial. Wakati wa usafirishaji, polypeptides sehemu unfolded ni imara na chaperones. Kwa kuongezea, chaperones hutimiza fungu muhimu katika kukusanyika kwa protini ambazo zina muundo tata, kama vile protini zenye vitengo vidogo vingi. Protini hizo zina minyororo mingi ya polypeptidi - ambayo kila moja inahitaji kukunjwa kwa usahihi na kisha kukusanywa kwa njia fulani hususa. Katika michakato inayohusika, chaperones husaidia katika kupindika protini na utulivu wa vipengele visivyounganishwa wakati sehemu nyingine za protini zinapokuwa zikikusanywa.