Chaperonin-mediated protein folding

The eukaryotic chaperonin TCP-1 ring complex (TRiC/ CCT) plays an essential role in the folding of a subset of proteins prominent among which are the actins and tubulins (reviewed in Altschuler and Willison, 2008). CCT/TRiC is an example of a type II chaperonin, defined (in contrast to type I) as functioning in the absence of a cochaperonin. TriC/CCT is a multisubunit toroidal complex that forms a cylinder containing two back-to-back stacked rings enclosing a cavity where substrate folding occurs in an ATP dependent process (reviewed in Altschuler and Willison, 2008 ). CCT/TriC contains eight paralogous subunits that are conserved throughout eukaryotic organisms (Leroux and Hartl 2000; Archibald et al. 2001; Valpuesta et al. 2002). CCT-mediated folding of non-native substrate protein involves capture through hydrophobic contacts with multiple chaperonin subunits followed by transfer of the protein into the central ring cavity where it folds. Although folding is initiated within this central cavity, only 5%-20% of proteins that are released have partitioned to the native state. The remaining portion is then recaptured by other chaperonin molecules (Cowan and Lewis 2001). This cycling process may be repeated multiple times before a target protein partitions to the native state. In the cell, binding to CCT occurs via presentation of target protein bound to upstream chaperones. During translation, the emerging polypeptide chain may be transferred from the ribosome to CCT via the chaperone Prefoldin (Vainberg et al., 1998) or the Hsp70 chaperone machinery (Melville et al., 2003). While the majority of CCT substrates ultimately partition to the native state as soluble, monomeric proteins, alpha and beta tubulin are unusual in that they require additional cofactors that are required to assemble the tubulin heterodimer (Cowan and Lewis 2001).

真核生物伴侣蛋白TCP-1环状复合物（TRiC/CCT）在蛋白质折叠过程中发挥着至关重要的作用，其中以肌动蛋白和微管蛋白等蛋白尤为显著（参见Altschuler和Willison，2008年的综述）。CCT/TRiC作为一种II型伴侣蛋白，与I型伴侣蛋白相对，其特征在于无需共伴侣蛋白即可发挥作用。TriC/CCT是一种多亚基的环状复合物，形成一个圆柱状结构，包含两个背靠背堆叠的环状结构，环状结构内部形成空腔，底物蛋白在此依赖ATP的过程中进行折叠（参见Altschuler和Willison，2008年的综述）。CCT/TriC包含八个在真核生物中保守的拟似物亚基（参见Leroux和Hartl，2000年；Archibald等，2001年；Valpuesta等，2002年）。CCT介导的非天然底物蛋白折叠过程涉及通过与多个伴侣蛋白亚基的疏水相互作用进行捕获，随后蛋白被转移到中央环状空腔中进行折叠。尽管折叠过程始于中央空腔，但只有5%-20%释放的蛋白达到天然状态。剩余的蛋白随后被其他伴侣蛋白分子重新捕获（参见Cowan和Lewis，2001年）。这种循环过程可能重复多次，直至目标蛋白达到天然状态。在细胞中，目标蛋白通过与上游伴侣蛋白的结合而与CCT结合。在翻译过程中，新出现的多肽链可能通过伴侣蛋白Prefoldin（参见Vainberg等，1998年）或Hsp70伴侣蛋白机制（参见Melville等，2003年）从核糖体转移到CCT。尽管大多数CCT底物最终以可溶性、单聚蛋白的形式达到天然状态，但α和β微管蛋白的独特之处在于它们需要额外的辅助因子，这些因子对于微管蛋白异二聚体的组装是必需的（参见Cowan和Lewis，2001年）。