Center for integrated protein science at the Department Chemie of the Technische Universität München, 84748, Garching, Germany.
Soft Matter Research Center and Department of Chemistry, Zhejiang University, Hangzhou, 310027, P.R. China.
Nat Commun. 2018 Apr 16;9(1):1472. doi: 10.1038/s41467-018-03946-x.
Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that undergoes large conformational changes during its functional cycle. It has been established that conformational switch points exist in the N-terminal (Hsp90-N) and C-terminal (Hsp90-C) domains of Hsp90, however information for switch points in the large middle-domain (Hsp90-M) is scarce. Here we report on a tryptophan residue in Hsp90-M as a new type of switch point. Our study shows that this conserved tryptophan senses the interaction of Hsp90 with a stringent client protein and transfers this information via a cation-π interaction with a neighboring lysine. Mutations at this position hamper the communication between domains and the ability of a client protein to affect the Hsp90 cycle. The residue thus allows Hsp90 to transmit information on the binding of a client from Hsp90-M to Hsp90-N which is important for progression of the conformational cycle and the efficient processing of client proteins.
热休克蛋白 90（Hsp90）是一种二聚体分子伴侣，在其功能循环中经历大的构象变化。已经确定 Hsp90 的 N 端（Hsp90-N）和 C 端（Hsp90-C）结构域中存在构象转换点，然而 Hsp90 中较大的中间结构域（Hsp90-M）的转换点信息很少。在这里，我们报告 Hsp90-M 中的一个色氨酸残基作为一种新的转换点。我们的研究表明，这个保守的色氨酸感知 Hsp90 与严格的客户蛋白的相互作用，并通过与相邻赖氨酸的阳离子-π 相互作用传递此信息。该位置的突变会阻碍结构域之间的通信以及客户蛋白影响 Hsp90 循环的能力。因此，该残基允许 Hsp90 将关于客户蛋白结合的信息从 Hsp90-M 传递到 Hsp90-N，这对于构象循环的进展和客户蛋白的有效处理很重要。
