Department of Biochemistry, School of Biology, Moscow State University, Moscow 119991, Russian Federation.
Curr Protein Pept Sci. 2012 Feb;13(1):76-85. doi: 10.2174/138920312799277875.
Small heat shock proteins (sHsp) form a large ubiquitous family of proteins expressed in all phyla of living organisms. The members of this family have low molecular masses (13-43 kDa) and contain a conservative α-crystallin domain. This domain (about 90 residues) consists of several β-strands forming two β-sheets packed in immunoglobulinlike manner. The α-crystallin domain plays an important role in formation of stable sHsp dimers, which are the building blocks of the large sHsp oligomers. A large N-terminal domain and a short C-terminal extension flank the α-crystallin domain. Both the N-terminal domain and the C-terminal extension are flexible, susceptible to proteolysis, prone to posttranslational modifications, and are predominantly intrinsically disordered. Differently oriented N-terminal domains interact with each other, with the core α-crystallin domain of the same or neighboring dimers and play important role in formation of large sHsp oligomers. Phosphorylation of certain sites in the N-terminal domain affects the sHsp quaternary structure, the sHsp interaction with target proteins and the sHsp chaperone-like activity. The C-terminal extension often carrying the conservative tripeptide (I/V/L)-X-(I/V/L) is capable of binding to a hydrophobic groove on the surface of the core α-crystallin domain of neighboring dimer, thus affecting the plasticity and the overall structure of sHsp oligomers. The Cterminal extension interacts with target proteins and affects their interaction with the α-crystallin domain increasing solubility of the complexes formed by sHsp and their targets. Thus, disordered N- and C-terminal sequences play important role in the structure, regulation and functioning of sHsp.
小分子热休克蛋白（sHsp）形成了一个广泛存在于所有生物门类的蛋白质大家族。该家族的成员具有低分子量（13-43 kDa），并含有保守的α-晶体蛋白结构域。这个结构域（约 90 个残基）由几个β-折叠组成，形成两个β-片层，以免疫球蛋白样的方式折叠。α-晶体蛋白结构域在形成稳定的 sHsp 二聚体中起着重要作用，二聚体是大 sHsp 寡聚物的构建块。一个大的 N 端结构域和一个短的 C 端延伸侧翼α-晶体蛋白结构域。N 端结构域和 C 端延伸都是灵活的，易受蛋白水解的影响，易发生翻译后修饰，并且主要是无序的。不同取向的 N 端结构域相互作用，与同一或相邻二聚体的核心α-晶体蛋白结构域相互作用，在大 sHsp 寡聚体的形成中起着重要作用。N 端结构域中某些位点的磷酸化会影响 sHsp 的四级结构、sHsp 与靶蛋白的相互作用以及 sHsp 的分子伴侣样活性。C 端延伸通常携带保守的三肽（I/V/L）-X-（I/V/L），能够与相邻二聚体核心α-晶体蛋白结构域表面的疏水凹槽结合，从而影响 sHsp 寡聚体的可塑性和整体结构。C 端延伸与靶蛋白相互作用，并影响它们与α-晶体蛋白结构域的相互作用，增加 sHsp 与其靶蛋白形成的复合物的溶解度。因此，无序的 N 端和 C 端序列在 sHsp 的结构、调节和功能中起着重要作用。
