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DOI | 10.1038/ncomms15172 |
Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1 | |
Xu, Wanping1; Beebe, Kristin1; Chavez, Juan D.2; Boysen, Marta3; Lu, YinYing1,7; Zuehlke, Abbey D.1; Keramisanou, Dimitra4; Trepel, Jane B.5; Prodromou, Christosomos6; Mayer, Matthias P.3; Bruce, James E.2; Gelis, Ioannis4; Neckers, Len1 | |
2019-06-12 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Germany; England; Peoples R China |
英文摘要 | Complex conformational dynamics are essential for function of the dimeric molecular chaperone heat shock protein 90 (Hsp90), including transient, ATP-biased N-domain dimerization that is necessary to attain ATPase competence. The intrinsic, but weak, ATP hydrolyzing activity of human Hsp90 is markedly enhanced by the co-chaperone Aha1. However, the cellular concentration of Aha1 is substoichiometric relative to Hsp90. Here we report that initial recruitment of this cochaperone to Hsp90 is markedly enhanced by phosphorylation of a highly conserved tyrosine (Y313 in Hsp90 alpha) in the Hsp90 middle domain. Importantly, phosphomimetic mutation of Y313 promotes formation of a transient complex in which both N- and C-domains of Aha1 bind to distinct surfaces of the middle domains of opposing Hsp90 protomers prior to ATP-directed N-domain dimerization. Thus, Y313 represents a phosphorylation-sensitive conformational switch, engaged early after client loading, that affects both local and long-range conformational dynamics to facilitate initial recruitment of Aha1 to Hsp90. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000471224100004 |
WOS关键词 | N-TERMINAL DOMAIN ; POSTTRANSLATIONAL MODIFICATIONS ; CHAPERONE ; BINDING ; PROTEIN ; ACTIVATION ; SENSITIVITY ; STATES ; P23 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203277 |
专题 | 资源环境科学 |
作者单位 | 1.NCI, Urol Oncol Branch, Bethesda, MD 20892 USA; 2.Univ Washington, Dept Genome Sci, Sch Med, Seattle, WA 98195 USA; 3.Heidelberg Univ, Ctr Mol Biol, D-69120 Heidelberg, Germany; 4.Univ S Florida, Dept Chem, Tampa, FL 33620 USA; 5.NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA; 6.Univ Sussex, Genome & Damage Stabil Ctr, Brighton BN1 9RH, E Sussex, England; 7.Beijing 302 Hosp, Ctr Therapeut Res Hepatocarcinoma, 100 Xi Si Huan Middle Rd, Beijing 100039, Peoples R China |
推荐引用方式 GB/T 7714 | Xu, Wanping,Beebe, Kristin,Chavez, Juan D.,et al. Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Xu, Wanping.,Beebe, Kristin.,Chavez, Juan D..,Boysen, Marta.,Lu, YinYing.,...&Neckers, Len.(2019).Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1.NATURE COMMUNICATIONS,10. |
MLA | Xu, Wanping,et al."Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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