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A Dynamic View of ATP-coupled Functioning Cycle of Hsp90 N-terminal Domain

文献类型：期刊论文

作者Zhang, Huaqun2; Zhou, Chen2; Chen, Wuyan1; Xu, Yechun1; Shi, Yanhong2; Wen, Yi2; Zhang, Naixia2,3
刊名SCIENTIFIC REPORTS
出版日期2015-04-13
卷号5
ISSN号2045-2322
DOI10.1038/srep09542
文献子类Article
英文摘要Heat-shock protein 90 (Hsp90) is one of the most important chaperones involved in multiple cellular processes. The chaperoning function of Hsp90 is intimately coupled to the ATPase activity presented by its N-terminal domain. However, the molecular mechanism for the ATP-dependent working cycle of Hsp90 is still not fully understood. In this study, we use NMR techniques to investigate the structural characteristics and dynamic behaviors of Hsp90 N-terminal domain in its free and AMPPCP (ATP analogue) or ADP-bound states. We demonstrated that although AMPPCP and ADP bind to almost the same region of Hsp90, significantly different effects on the dynamics behaviors of the key structural elements were observed. AMPPCP binding favors the formation of the active homodimer of Hsp90 by enhancing the slow-motion featured conformational exchanges of those residues (A117-A141) within the lid segment (A111-G135) and around region, while ADP binding keeps Hsp90 staying at the inactive state by increasing the conformational rigidity of the lid segment and around region. Based on our findings, a dynamic working model for the ATP-dependent functioning cycle of Hsp90 was proposed.
WOS关键词NUCLEAR-MAGNETIC-RESONANCE ; PROTEIN SECONDARY STRUCTURE ; CHEMICAL-SHIFT INDEX ; MODEL-FREE APPROACH ; MOLECULAR CHAPERONE ; CANCER-THERAPY ; SIGNAL-TRANSDUCTION ; BREAST-CANCER ; RELAXATION ; BINDING
资助项目National Natural Science Foundation of China[21272246] ; National Natural Science Foundation of China[31300608] ; National Natural Science Foundation of China[81330076] ; Chinese Academy of Sciences (100 Talents Program)[00000000] ; National Key Basic Research Program of China[2013CB910900] ; Chinese Academy of Sciences (Technology Innovation Project)[00000000]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000352723000001
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/276573]  
专题分析化学研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药物发现与设计中心
通讯作者Chen, Wuyan
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Key Lab Receptor Res, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Huaqun,Zhou, Chen,Chen, Wuyan,et al. A Dynamic View of ATP-coupled Functioning Cycle of Hsp90 N-terminal Domain[J]. SCIENTIFIC REPORTS,2015,5.
APA Zhang, Huaqun.,Zhou, Chen.,Chen, Wuyan.,Xu, Yechun.,Shi, Yanhong.,...&Zhang, Naixia.(2015).A Dynamic View of ATP-coupled Functioning Cycle of Hsp90 N-terminal Domain.SCIENTIFIC REPORTS,5.
MLA Zhang, Huaqun,et al."A Dynamic View of ATP-coupled Functioning Cycle of Hsp90 N-terminal Domain".SCIENTIFIC REPORTS 5(2015).

入库方式： OAI收割

来源：上海药物研究所

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