The Chaperone Activity of the Developmental Small Heat Shock Protein Sip1 Is Regulated by pH-Dependent Conformational Changes
The Chaperone Activity of the Developmental Small Heat Shock Protein Sip1 Is Regulated by pH-Dependent Conformational Changes
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DOI：
10.1016/j.molcel.2015.04.019
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发表时间：
2015-06-18
期刊：
影响因子：
16
通讯作者：
Buchner, Johannes
中科院分区：
文献类型：
--
作者：
Fleckenstein, Tilly;Kastenmueller, Andreas;Buchner, Johannes
小热休克蛋白 (sHsps) 是普遍存在的分子伴侣，可防止蛋白毒性应激期间未折叠蛋白的聚集。在秀丽隐杆线虫中，Sip1 是唯一在卵母细胞和胚胎中专门表达的 sHsp。在这里，我们证明 Sip1 对于繁殖的成体和胚胎的热休克存活至关重要。 X射线晶体学和电子显微镜显示，Sip1存在于一系列明确的球状组件中，该组件由两个半球组成，每个半球由二聚体“辐条”组成。引人注目的是，Sip1的寡聚分布及其伴侣活性取决于pH值，其物种趋向于更小，而在酸性条件下（例如在线虫卵中存在）活性更高。相互作用组的分析表明，Sip1具有特定的底物谱，包括对胚胎发育至关重要的蛋白质。
Small heat shock proteins (sHsps) are ubiquitous molecular chaperones that prevent the aggregation of unfolding proteins during proteotoxic stress. In Caenorhabditis elegans, Sip1 is the only sHsp exclusively expressed in oocytes and embryos. Here, we demonstrate that Sip1 is essential for heat shock survival of reproducing adults and embryos. X-ray crystallography and electron microscopy revealed that Sip1 exists in a range of well-defined globular assemblies consisting of two half-spheres, each made of dimeric "spokes.'' Strikingly, the oligomeric distribution of Sip1 as well as its chaperone activity depend on pH, with a trend toward smaller species and higher activity at acidic conditions such as present in nematode eggs. The analysis of the interactome shows that Sip1 has a specific substrate spectrum including proteins that are essential for embryo development.