The crystal structure of yeast CCT reveals intrinsic asymmetry of eukaryotic cytosolic chaperonins
The crystal structure of yeast CCT reveals intrinsic asymmetry of eukaryotic cytosolic chaperonins
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DOI：
10.1038/emboj.2011.208
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发表时间：
2011-08-03
期刊：
影响因子：
11.4
通讯作者：
Willison, Keith R.
中科院分区：
文献类型：
--
作者：
Dekker, Carien;Roe, S. Mark;Willison, Keith R.
胞质伴侣蛋白CCT是真核生物必需的1-MDa蛋白质折叠机器。CCT相互作用组显示参与小范围蛋白质的折叠和组装，这些蛋白质与细胞骨架组装和细胞周期调控等基本细胞过程相关。CCT具有经典的伴侣蛋白结构，具有两个背靠背堆叠的异质8元环，包围折叠腔。然而，CCT辅助折叠的机制与其他伴侣蛋白不同，没有疏水壁内衬潜在的Anfinsen笼，以及顺序而不是协调的ATP水解机制。我们已经解决了晶体结构的酵母CCT在复杂的肌动蛋白在3.8埃的分辨率，揭示了亚基组织和位置的离散补丁的共同发展的“签名残基”，介导特定的相互作用之间的CCT和它的基板。CCT亚基的结构个体性揭示了内在的不对称性，CCT亚基显示出独特的构型、底物结合特性、ATP结合异质性和亚基-亚基相互作用。突变研究证实，进化上保守的N-末端的Cct 5的桶外的位置，是唯一的真核细胞胞质伴侣蛋白。The EMBO Journal（2011）30，3078-3090. doi：10.1038/daj.2011.208; 2011年6月24日在线发布
The cytosolic chaperonin CCT is a 1-MDa protein-folding machine essential for eukaryotic life. The CCT interactome shows involvement in folding and assembly of a small range of proteins linked to essential cellular processes such as cytoskeleton assembly and cell-cycle regulation. CCT has a classic chaperonin architecture, with two heterogeneous 8-membered rings stacked back-to-back, enclosing a folding cavity. However, the mechanism by which CCT assists folding is distinct from other chaperonins, with no hydrophobic wall lining a potential Anfinsen cage, and a sequential rather than concerted ATP hydrolysis mechanism. We have solved the crystal structure of yeast CCT in complex with actin at 3.8 angstrom resolution, revealing the subunit organisation and the location of discrete patches of co-evolving 'signature residues' that mediate specific interactions between CCT and its substrates. The intrinsic asymmetry is revealed by the structural individuality of the CCT subunits, which display unique configurations, substrate binding properties, ATP-binding heterogeneity and subunit-subunit interactions. The location of the evolutionarily conserved N-terminus of Cct5 on the outside of the barrel, confirmed by mutational studies, is unique to eukaryotic cytosolic chaperonins. The EMBO Journal (2011) 30, 3078-3090. doi:10.1038/emboj.2011.208; Published online 24 June 2011