An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans.
An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans.
复制标题
酵母中的 Hsp90 共伴侣蛋白在功能上被人类中的位点特异性翻译后修饰所取代。
DOI：
10.1038/ncomms15328
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发表时间：
2017
影响因子：
16.6
通讯作者：
Neckers,Len
中科院分区：
文献类型：
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作者：
Zuehlke,AbbeyD;Reidy,Michael;Lin,Coney;LaPointe,Paul;Alsomairy,Sarah;Lee,DJoshua;Rivera-Marquez,GenesisM;Beebe,Kristin;Prince,Thomas;Lee,Sunmin;Trepel,JaneB;Xu,Wanping;Johnson,Jill;Masison,Daniel;Neckers,Len
热休克蛋白90 （Hsp90）是真核生物必不可少的分子伴侣。为了正确地陪伴其客户，Hsp90通过atp依赖的构象周期进行，该周期受翻译后修饰（ptm）的影响，并由许多共同伴侣蛋白辅助。尽管Hsp90在溶液中的构象变化已经得到了很好的研究，但细胞中这些复杂动力学的调控仍不清楚。人类Hsp90α在高度保守的酪氨酸627位点的磷酸化，此前曾报道过会减少客户端相互作用和Aha1结合。在这里，我们报告了这些影响是由于远程构象影响抑制Hsp90α n -结构域二聚化，并且涉及先前被认为是底物结合位点的中间结构域/羧基末端结构域界面区域。虽然Y627在酵母中不被磷酸化，但我们证明了非保守的酵母共伴侣蛋白Hch1类似地影响酵母Hsp90 （Hsp82）的构象和功能，这提高了这种PTM在高等真核生物中的出现代表Hch1的进化替代的可能性。
Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone. To properly chaperone its clientele, Hsp90 proceeds through an ATP-dependent conformational cycle influenced by posttranslational modifications (PTMs) and assisted by a number of co-chaperone proteins. Although Hsp90 conformational changes in solution have been well-studied, regulation of these complex dynamics in cells remains unclear. Phosphorylation of human Hsp90α at the highly conserved tyrosine 627 has previously been reported to reduce client interaction and Aha1 binding. Here we report that these effects are due to a long-range conformational impact inhibiting Hsp90α N-domain dimerization and involving a region of the middle domain/carboxy-terminal domain interface previously suggested to be a substrate binding site. Although Y627 is not phosphorylated in yeast, we demonstrate that the non-conserved yeast co-chaperone, Hch1, similarly affects yeast Hsp90 (Hsp82) conformation and function, raising the possibility that appearance of this PTM in higher eukaryotes represents an evolutionary substitution forHCH1.