Substrate Binding Switches the Conformation at the Lynchpin Site in the Substrate-Binding Domain of Human Hsp70 to Enable Allosteric Interdomain Communication.
Substrate Binding Switches the Conformation at the Lynchpin Site in the Substrate-Binding Domain of Human Hsp70 to Enable Allosteric Interdomain Communication.
复制标题
底物结合在人类HSP70的底物结合域中的Lynchpin位点的构象开关，以实现变构层间通信。
DOI：
10.3390/molecules23030528
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发表时间：
2018-02-27
期刊：
影响因子：
--
通讯作者：
Tate SI
中科院分区：
文献类型：
--
作者：
Umehara K;Hoshikawa M;Tochio N;Tate SI
应激诱导的70 kDa热休克蛋白（Hsp 70）作为分子伴侣维持蛋白质稳态。热休克蛋白70含有N端ATP酶结构域（NBD）和C端底物结合结构域（SBD）。SBD分为含有底物结合位点的β亚结构域（βSBD）和覆盖βSBD的α-螺旋亚结构域（αLid）。在本报告中，解决了两种不同形式的SBD从人Hsp 70的溶液结构。一种结构显示αLid以分子内方式结合于底物结合位点，而另一种结构中不存在这种分子内结合模式。从热休克蛋白70的两个SBD的结构比较表明，客户端肽结合重排的域间接触位点，这损害了SBD和NBD之间的域间接触的残基。肽结合还破坏了连接αLid与βSBD的亚结构域间相互作用，这允许αLid与NBD结合。这些结果为Hsp 70的βSBD与NBD通过lynchpin位点的底物结合提供了结构域间通讯的机制。与细菌直向同源物DnaK相比，Hsp 70 SBD内残基之间的变构信号传播存在一些显着差异。
The stress-induced 70 kDa heat shock protein (Hsp70) functions as a molecular chaperone to maintain protein homeostasis. Hsp70 contains an N-terminal ATPase domain (NBD) and a C-terminal substrate-binding domain (SBD). The SBD is divided into the β subdomain containing the substrate-binding site (βSBD) and the α-helical subdomain (αLid) that covers the βSBD. In this report, the solution structures of two different forms of the SBD from human Hsp70 were solved. One structure shows the αLid bound to the substrate-binding site intramolecularly, whereas this intramolecular binding mode is absent in the other structure solved. Structural comparison of the two SBDs from Hsp70 revealed that client-peptide binding rearranges residues at the interdomain contact site, which impairs interdomain contact between the SBD and the NBD. Peptide binding also disrupted the inter-subdomain interaction connecting the αLid to the βSBD, which allows the binding of the αLid to the NBD. The results provide a mechanism for interdomain communication upon substrate binding from the SBD to the NBD via the lynchpin site in the βSBD of human Hsp70. In comparison to the bacterial ortholog, DnaK, some remarkable differences in the allosteric signal propagation among residues within the Hsp70 SBD exist.
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影响因子：
4.8
作者：
Buczynski, G;Slepenkov, SV;Witt, SN
通讯作者：
Witt, SN
影响因子：
4
作者：
Leu, Julia I-Ju;Zhang, Pingfeng;Murphy, Maureen E.;Marmorstein, Ronen;George, Donna L.
通讯作者：
George, Donna L.
影响因子：
16
作者：
Kityk, Roman;Kopp, Juergen;Mayer, Matthias P.
通讯作者：
Mayer, Matthias P.
影响因子：
3.4
作者：
Brocchieri L;Conway de Macario E;Macario AJ
通讯作者：
Macario AJ
DOI：
10.1073/pnas.0903503106
发表时间：
2009-05-26
影响因子：
11.1
作者：
Bertelsen, Eric B.;Chang, Lyra;Zuiderweg, Erik R. P.
通讯作者：
Zuiderweg, Erik R. P.