Munich Center for Integrated Protein Science and Department Chemie Technische Universität München, Garching, Germany.
FASEB J. 2010 Oct;24(10):3633-42. doi: 10.1096/fj.10-156992. Epub 2010 May 25.
Small heat shock proteins (sHsps) are molecular chaperones involved in maintaining protein homeostasis; they have also been implicated in protein folding diseases and in cancer. In this protein family, a conserved core domain, the so-called α-crystallin or Hsp20 domain, is flanked by highly variable, nonconserved sequences that are essential for chaperone function. Analysis of 8714 sHsps revealed a broad variation of primary sequences within the superfamily as well as phyla-dependent differences. Significant variations were found in the number of sHsps per genome, their amino acid composition, and the length distribution of the different sequence parts. Reconstruction of the evolutionary tree for the sHsp superfamily shows that the flanking regions fall into several subgroups, indicating that they were remodeled several times in parallel but independent of the evolution of the α-crystallin domain. The evolutionary history of sHsps is thus set apart from that of other protein families in that two exon boundary-independent strategies are combined: the evolution of the conserved α-crystallin domain and the independent evolution of the N- and C-terminal sequences. This scenario allows for increased variability in specific small parts of the protein and thus promotes functional and structural differentiation of sHsps, which is not reflected in the general evolutionary tree of species.
小分子热休克蛋白（sHsps）是参与维持蛋白质平衡的分子伴侣；它们也与蛋白质折叠疾病和癌症有关。在这个蛋白质家族中，一个保守的核心结构域，即所谓的α-晶状体蛋白或 HSP20 结构域，被高度可变的非保守序列包围，这些序列对于伴侣功能至关重要。对 8714 种 sHsps 的分析揭示了超家族内广泛的序列变化以及门依赖性差异。每个基因组中的 sHsps 数量、其氨基酸组成以及不同序列部分的长度分布都存在显著差异。sHsp 超家族的进化树重建表明，侧翼区域分为几个亚组，表明它们在平行但独立于 α-晶状体蛋白结构域进化的情况下多次重塑。因此，sHsps 的进化历史与其他蛋白质家族的进化历史不同，因为它结合了两种独立于外显子边界的策略：保守的α-晶状体蛋白结构域的进化和 N 端和 C 端序列的独立进化。这种情况允许蛋白质特定小部分的可变性增加，从而促进 sHsps 的功能和结构分化，这在物种的一般进化树中没有反映出来。
