Ranson Neil A, Clare Daniel K, Farr George W, Houldershaw David, Horwich Arthur L, Saibil Helen R
Astbury Centre for Structural Molecular Biology and Institute of Molecular & Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Nat Struct Mol Biol. 2006 Feb;13(2):147-52. doi: 10.1038/nsmb1046. Epub 2006 Jan 22.
The double-ring chaperonin GroEL and its lid-like cochaperonin GroES form asymmetric complexes that, in the ATP-bound state, mediate productive folding in a hydrophilic, GroES-encapsulated chamber, the so-called cis cavity. Upon ATP hydrolysis within the cis ring, the asymmetric complex becomes able to accept non-native polypeptides and ATP in the open, trans ring. Here we have examined the structural basis for this allosteric switch in activity by cryo-EM and single-particle image processing. ATP hydrolysis does not change the conformation of the cis ring, but its effects are transmitted through an inter-ring contact and cause domain rotations in the mobile trans ring. These rigid-body movements in the trans ring lead to disruption of its intra-ring contacts, expansion of the entire ring and opening of both the nucleotide pocket and the substrate-binding domains, admitting ATP and new substrate protein.
双环伴侣蛋白GroEL及其类似盖子的共伴侣蛋白GroES形成不对称复合物，在ATP结合状态下，该复合物在亲水性的、由GroES包裹的腔室（即所谓的顺式腔）中介导有效的折叠过程。当顺式环内发生ATP水解时，不对称复合物能够在开放的反式环中接受非天然多肽和ATP。在这里，我们通过冷冻电镜和单颗粒图像处理研究了这种活性变构转换的结构基础。ATP水解不会改变顺式环的构象，但其效应通过环间接触传递，导致可移动的反式环中的结构域旋转。反式环中的这些刚体运动导致其环内接触的破坏、整个环的扩张以及核苷酸口袋和底物结合结构域的开放，从而允许ATP和新的底物蛋白进入。
