Insights into the molecular mechanism of allostery in Hsp70s.
Insights into the molecular mechanism of allostery in Hsp70s.
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DOI：
10.3389/fmolb.2015.00058
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发表时间：
2015
影响因子：
5
通讯作者：
Kityk R
中科院分区：
文献类型：
--
作者：
Mayer MP;Kityk R
热休克蛋白70分子伴侣蛋白的数量和种类惊人的细胞蛋白质折叠过程。其多功能性的关键是识别几乎所有多肽中存在的短简并序列基序，以及连接其N-末端核苷酸结合结构域（NBD）和其C-末端多肽底物结合结构域（SBD）的双向变构分子内调节机制。通过这种结构域间通讯，ATP与NBD的结合和ATP水解控制SBD对多肽底物的亲和力，底物与SBD的结合触发ATP水解。Hsp 70缺陷变体的遗传筛选和对分离结构域可用结构的系统分析揭示了一些参与变构控制的残基。最近阐明的热休克蛋白70同系物DnaK的ATP结合的开放构象的晶体结构，以及众多的NMR和诱变研究使我们更接近NBD和SBD之间的通信的理解。本文就热休克蛋白70分子伴侣的变构调控机制进行综述。
Hsp70s chaperone an amazing number and variety of cellular protein folding processes. Key to their versatility is the recognition of a short degenerate sequence motif, present in practically all polypeptides, and a bidirectional allosteric intramolecular regulation mechanism linking their N-terminal nucleotide binding domain (NBD) and their C-terminal polypeptide substrate binding domain (SBD). Through this interdomain communication ATP binding to the NBD and ATP hydrolysis control the affinity of the SBD for polypeptide substrates and substrate binding to the SBD triggers ATP hydrolysis. Genetic screens for defective variants of Hsp70s and systematic analysis of available structures of the isolated domains revealed some residues involved in allosteric control. Recent elucidation of the crystal structure of the Hsp70 homolog DnaK in the ATP bound open conformation as well as numerous NMR and mutagenesis studies bring us closer to an understanding of the communication between NBD and SBD. In this review we will discuss our current view of the allosteric control mechanism of Hsp70 chaperones.