Synoradzki Kamil, Bieganowski Pawel
Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., Warsaw 02-106, Poland.
Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., Warsaw 02-106, Poland.
Biochim Biophys Acta. 2015 Feb;1853(2):445-52. doi: 10.1016/j.bbamcr.2014.11.026. Epub 2014 Dec 5.
Hsp90 is an essential chaperone for more than 200 client proteins in eukaryotic cells. The human genome encodes two highly similar cytosolic Hsp90 proteins called Hsp90α and Hsp90β. Most of the client proteins can interact with either Hsp90 protein; however, only a handful client proteins and one co-chaperone that interact specifically with one of the Hsp90 isoforms were identified. Structural differences underlying these isoform-specific interactions were not studied. Here we report for the first time that the Hsp90 co-chaperone Aha1 interacts preferentially with Hsp90α. The distinction depends on the middle domain of Hsp90. The middle domain of Hsp90α is also responsible for the slow growth phenotype of yeasts that express this isoform as a sole source of Hsp90. These results suggest that differences in the middle domain of Hsp90α and Hsp90β may be responsible for the isoform-specific interactions with selected proteins. Also shown here within, we determine that preferential chaperoning of cIAP1 by Hsp90β is mediated by the N-terminal domain of this isoform.
热休克蛋白90（Hsp90）是真核细胞中200多种客户蛋白的必需伴侣蛋白。人类基因组编码两种高度相似的胞质Hsp90蛋白，分别称为Hsp90α和Hsp90β。大多数客户蛋白可以与任何一种Hsp90蛋白相互作用；然而，仅鉴定出少数几种与其中一种Hsp90亚型特异性相互作用的客户蛋白和一种共伴侣蛋白。尚未研究这些亚型特异性相互作用背后的结构差异。在此，我们首次报道Hsp90共伴侣蛋白Aha1优先与Hsp90α相互作用。这种区别取决于Hsp90的中间结构域。Hsp90α的中间结构域也是将该亚型作为Hsp90唯一来源表达的酵母生长缓慢表型的原因。这些结果表明，Hsp90α和Hsp90β中间结构域的差异可能是与选定蛋白发生亚型特异性相互作用的原因。我们还在此确定，Hsp90β对细胞凋亡抑制蛋白1（cIAP1）的优先伴侣作用是由该亚型的N端结构域介导的。
