Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, U.S.A.
Biochem Soc Trans. 2022 Oct 31;50(5):1403-1414. doi: 10.1042/BST20220591.
The cytosolic chaperonin CCT is indispensable to eukaryotic life, folding the cytoskeletal proteins actin and tubulin along with an estimated 10% of the remaining proteome. However, it also participates in human diseases such as cancer and viral infections, rendering it valuable as a potential therapeutic target. CCT consists of two stacked rings, each comprised of eight homologous but distinct subunits, that assists the folding of a remarkable substrate clientele that exhibits both broad diversity and specificity. Much of the work in recent years has been aimed at understanding the mechanisms of CCT substrate recognition and folding. These studies have revealed new binding sites and mechanisms by which CCT uses its distinctive subunit arrangement to fold structurally unrelated substrates. Here, we review recent structural insights into CCT-substrate interactions and place them into the broader context of CCT function and its implications for human health.
细胞质伴侣蛋白 CCT 对于真核生物的生命活动是不可或缺的，它可以折叠细胞骨架蛋白肌动蛋白和微管蛋白，以及估计 10%的其余蛋白质组。然而，它也参与人类疾病，如癌症和病毒感染，使其成为有价值的潜在治疗靶点。CCT 由两个堆叠的环组成，每个环由八个同源但不同的亚基组成，有助于折叠具有广泛多样性和特异性的显著底物。近年来的大部分工作旨在理解 CCT 底物识别和折叠的机制。这些研究揭示了 CCT 利用其独特的亚基排列来折叠结构上不相关的底物的新的结合位点和机制。在这里，我们回顾了 CCT-底物相互作用的最新结构见解，并将其置于 CCT 功能的更广泛背景及其对人类健康的影响中。
