Three-Dimensional Structure of α-Crystallin Domain Dimers of Human Small Heat Shock Proteins HSPB1 and HSPB6
Three-Dimensional Structure of α-Crystallin Domain Dimers of Human Small Heat Shock Proteins HSPB1 and HSPB6
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DOI：
10.1016/j.jmb.2011.05.024
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发表时间：
2011-08-05
影响因子：
5.6
通讯作者：
Strelkov, S. V.
中科院分区：
文献类型：
--
作者：
Baranova, E. V.;Weeks, S. D.;Strelkov, S. V.
小分子热休克蛋白（Small heat shock proteins，sHSPs）是一类进化上保守的不依赖ATP的分子伴侣。这些蛋白质共享由两侧具有高度可变的N-和C-末端延伸的签名α-晶状体蛋白结构域（ACD）定义的共同结构。具有免疫球蛋白样折叠的ACD在sHSP组装中起重要作用。该结构域介导单个原聚体的二聚体形成，然后可以组装成更大的寡聚体。在脊椎动物sHSP中，二聚体界面由两条β-链的对称反平行配对形成（137），在ACD二聚体的一面上产生延伸的β-折叠。最近对来自许多脊椎动物sHSP的分离的ACD的结构研究表明β 7/β 7链界面的寄存器的可变性，这可能部分地引起通常与全长蛋白质相关的多分散性。为了进一步分析ACD二聚体的结构，我们采用了X射线晶体学和溶液小角X射线散射（SAXS）的组合来研究人HSPB 1（HSP 27）和HSPB 6（HSP 20）的含ACD片段。出乎意料的是，所获得的HSPB 1片段的晶体结构没有显示出典型的β 7/β 7二聚体，而是由来自相邻ACD的β 4和β 7链之间的不对称接触形成的六聚体。然而，在溶液中，两种ACD通过β 7链的对称反对位相互作用形成稳定的二聚体。使用SAXS，我们表明，它是可以区分不同的推定寄存器的β 7/β 7接口，结果表明，在生理条件下，只有一个单一的寄存器的两种蛋白质的链。(C)2011爱思唯尔有限公司保留所有权利。
Small heat shock proteins (sHSPs) are a family of evolutionary conserved ATP-independent chaperones. These proteins share a common architecture defined by a signature alpha-crystallin domain (ACD) flanked by highly variable N- and C-terminal extensions. The ACD, which has an immunoglobulin-like fold, plays an important role in sHSP assembly. This domain mediates dimer formation of individual protomers, which then may assemble into larger oligomers. In vertebrate sHSPs, the dimer interface is formed by the symmetrical antiparallel pairing of two beta-strands (137), generating an extended beta-sheet on one face of the ACD dimer. Recent structural studies of isolated ACDs from a number of vertebrate sHSPs suggest a variability in the register of the beta 7/beta 7 strand interface, which may, in part, give rise to the polydispersity often associated with the full-length proteins. To further analyze the structure of ACD dimers, we have employed a combination of X-ray crystallography and solution small-angle X-ray scattering (SAXS) to study the ACD-containing fragments of human HSPB1 (HSP27) and HSPB6 (HSP20). Unexpectedly, the obtained crystal structure of the HSPB1 fragment does not reveal the typical beta 7/beta 7 dimers but, rather, hexamers formed by an asymmetric contact between the beta 4 and the beta 7 strands from adjacent ACDs. Nevertheless, in solution, both ACDs form stable dimers via the symmetric antiparaLlel interaction of beta 7 strands. Using SAXS, we show that it is possible to discriminate between different putative registers of the beta 7/beta 7 interface, with the results indicating that, under physiological conditions, there is only a single register of the strands for both proteins. (C) 2011 Elsevier Ltd. All rights reserved.