Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle
Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle
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DOI：
10.1038/emboj.2011.366
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发表时间：
2012-02-01
期刊：
影响因子：
11.4
通讯作者：
Chiu, Wah
中科院分区：
文献类型：
--
作者：
Cong, Yao;Schroeder, Gunnar F.;Chiu, Wah
真核 II 族伴侣蛋白 TRiC/CCT 是一个 16 个亚基复合物，其中八个不同但相似的亚基排列在两个堆叠环中。中央室内的底物折叠是由 ATP 水解触发的。我们展示了处于 apo 和核苷酸诱导状态的 TRiC 的五种冷冻电镜结构，在 3D 重建过程中没有强加对称性。这些结构揭示了 ATP 酶循环期间环内和环间亚基相互作用模式的变化。在apo状态下，每个环中的亚基排列是高度不对称的，而所有含核苷酸的状态往往更加对称。我们鉴定并结构表征了由 ATP 水解诱导的单环闭合中间体，其中闭合 TRiC 环表现出可观察到的室膨胀。这可能代表生理基质折叠状态。我们的结构结果表明了 TRiC 环间负协同性、环内正协同性和蛋白质折叠室关闭的机制。有趣的是，这些机制与其他 I 组和 II 组伴侣蛋白不同，尽管它们具有相似的结构。 EMBO 杂志 (2012) 31, 720-730。 doi：10.1038/emboj.2011.366； 2011 年 11 月 1 日在线发布
The eukaryotic group II chaperonin TRiC/CCT is a 16-subunit complex with eight distinct but similar subunits arranged in two stacked rings. Substrate folding inside the central chamber is triggered by ATP hydrolysis. We present five cryo-EM structures of TRiC in apo and nucleotide-induced states without imposing symmetry during the 3D reconstruction. These structures reveal the intra- and inter-ring subunit interaction pattern changes during the ATPase cycle. In the apo state, the subunit arrangement in each ring is highly asymmetric, whereas all nucleotide-containing states tend to be more symmetrical. We identify and structurally characterize an one-ring closed intermediate induced by ATP hydrolysis wherein the closed TRiC ring exhibits an observable chamber expansion. This likely represents the physiological substrate folding state. Our structural results suggest mechanisms for inter-ring-negative cooperativity, intra-ring-positive cooperativity, and protein-folding chamber closure of TRiC. Intriguingly, these mechanisms are different from other group I and II chaperonins despite their similar architecture. The EMBO Journal (2012) 31, 720-730. doi: 10.1038/emboj.2011.366; Published online 1 November 2011