Liu Liang, Chen Jiyun, Yang Bo, Wang Yonghua
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
Institute of Systems Biomedicine and Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Biochem Biophys Res Commun. 2015 Mar 6;458(2):429-34. doi: 10.1016/j.bbrc.2015.01.134. Epub 2015 Feb 7.
Small heat shock proteins (sHSPs) are ubiquitous chaperones that play a vital role in protein homeostasis. sHSPs are characterized by oligomeric architectures and dynamic exchange of subunits. The flexible oligomeric assembling associating with function remains poorly understood. Based on the structural data, it is certainly agreed that two dimerization models depend on the presence or absence of a β6 strand to differentiate nonmetazoan sHSPs from metazoan sHSPs. Here, we report the Sulfolobus solfataricus Hsp20.1 ACD dimer structure, which shows a distinct dimeric interface. We observed that, in the absence of β6, Hsp20.1 dimer does not depend on β7 strand for forming dimer interface as metazoan sHSPs, nor dissociates to monomers. This is in contrast to other published sHSPs. Our structure reveals a variable, highly polar dimer interface that has advantages for rapid subunits exchange and substrate binding. Remarkably, we find that the C-terminal truncation variant has chaperone activity comparable to that of wild-type despite lack of the oligomer structure. Our further study indicates that the N-terminal region is essential for the oligomer and dimer binding to the target protein. Together, the structure and function of Hsp20.1 give more insight into the thermal protection mechanism of sHSPs.
小热休克蛋白（sHSPs）是普遍存在的伴侣蛋白，在蛋白质稳态中发挥着至关重要的作用。sHSPs的特点是具有寡聚结构和亚基的动态交换。与功能相关的灵活寡聚组装仍知之甚少。基于结构数据，可以肯定的是，两种二聚化模型取决于β6链的有无，以区分后生动物的sHSPs和非后生动物的sHSPs。在此，我们报道了嗜热栖热菌Hsp20.1 ACD二聚体结构，该结构显示出独特的二聚体界面。我们观察到，在没有β6的情况下，Hsp20.1二聚体不像后生动物的sHSPs那样依赖β7链来形成二聚体界面，也不会解离成单体。这与其他已发表的sHSPs不同。我们的结构揭示了一个可变的、高度极性的二聚体界面，这有利于亚基的快速交换和底物结合。值得注意的是，我们发现C末端截短变体尽管缺乏寡聚体结构，但具有与野生型相当的伴侣活性。我们的进一步研究表明，N末端区域对于寡聚体和二聚体与靶蛋白的结合至关重要。总之，Hsp20.1的结构和功能为深入了解sHSPs的热保护机制提供了更多线索。
