2019年9月19日，美国圣犹大儿童研究医院Charalampos G. Kalodimos课题组在《科学》杂志发表论文，揭示了Hsp40分子伴侣底物识别和活性调控的结构基础。

研究人员使用核磁共振光谱法来确定Hsp40与未折叠底物蛋白形成复合物后的溶液结构和动态特征。底物与Hsp40结合结构域复合后各个结合位点的原子结构揭示了识别模式。Hsp40使用改变底物折叠属性的多价结合机制以高度动态的方式结合底物。不同的Hsp40家族成员具有不同数量的底物结合位点且序列选择性不同，这为活性调节和功能修饰提供了额外的机制。Hsp70与Hsp40的结合取代了未折叠的底物。Hsp40的活性在其与Hsp70结合后被改变，从而进一步调节底物的结合与释放。

据介绍，Hsp70和Hsp40分子伴侣蛋白在多种生物过程中协同作用，包括蛋白质合成、膜转运和折叠。

附：英文原文

Title: Structural basis for client recognition and activity of Hsp40 chaperones

Author: Yajun Jiang, Paolo Rossi, Charalampos G. Kalodimos

Issue&Volume: Volume 365 Issue 6459

Abstract: 

Hsp70 and Hsp40 chaperones work synergistically in a wide range of biological processes including protein synthesis, membrane translocation, and folding. We used nuclear magnetic resonance spectroscopy to determine the solution structure and dynamic features of an Hsp40 in complex with an unfolded client protein. Atomic structures of the various binding sites in the client complexed to the binding domains of the Hsp40 reveal the recognition pattern. Hsp40 engages the client in a highly dynamic fashion using a multivalent binding mechanism that alters the folding properties of the client. Different Hsp40 family members have different numbers of client-binding sites with distinct sequence selectivity, providing additional mechanisms for activity regulation and function modification. Hsp70 binding to Hsp40 displaces the unfolded client. The activity of Hsp40 is altered in its complex with Hsp70, further regulating client binding and release.

DOI: 10.1126/science.aax1280

Source:https://science.sciencemag.org/content/365/6459/1313