Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity

doi:10.3390/molecules26071943

	Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity
	Hu, Huifang 1,2; Wang, Qing 2,3; Du, Jingwen 1,2; Liu, Zhijun 4; Ding, Yiluan 1; Xue, Hongjuan 4; Zhou, Chen 1; Feng, Linyin 2,3; Zhang, Naixia 1,2
刊名	MOLECULES
	2021-04-01
卷号	26 期号:7 页码:20
关键词	Aha1 NMR dynamics chaperone-like activity α -synuclein
DOI	10.3390/molecules26071943
通讯作者	Zhou, Chen(czhou@simm.ac.cn) ; Feng, Linyin(lyfeng@simm.ac.cn) ; Zhang, Naixia(nxzhang@simm.ac.cn)
英文摘要	Aha1 is the only co-chaperone known to strongly stimulate the ATPase activity of Hsp90. Meanwhile, besides the well-studied co-chaperone function, human Aha1 has also been demonstrated to exhibit chaperoning activity against stress-denatured proteins. To provide structural insights for a better understanding of Aha1's co-chaperone and chaperone-like activities, nuclear magnetic resonance (NMR) techniques were used to reveal the unique structure and internal dynamics features of full-length human Aha1. We then found that, in solution, both the two domains of Aha1 presented distinctive thermal stabilities and dynamics behaviors defined by their primary sequences and three-dimensional structures. The low thermal stability (melting temperature of Aha1(28-162): 54.45 degrees C) and the internal dynamics featured with slow motions on the mu s-ms time scale were detected for Aha1's N-terminal domain (Aha1N). The aforementioned experimental results suggest that Aha1N is in an energy-unfavorable state, which would therefore thermostatically favor the interaction of Aha1N with its partner proteins such as Hsp90's middle domain. Differently from Aha1N, Aha1C (Aha1's C-terminal domain) exhibited enhanced thermal stability (melting temperature of Aha1(204-335): 72.41 degrees C) and the internal dynamics featured with intermediate motions on the ps-ns time scale. Aha1C's thermal and structural stabilities make it competent for the stabilization of the exposed hydrophobic groove of dimerized Hsp90's N-terminal domain. Of note, according to the NMR data and the thermal shift results, although the very N-terminal region (M1-W27) and the C-terminal relaxin-like factor (RLF) motif showed no tight contacts with the remaining parts of human Aha1, they were identified to play important roles in the recognition of intrinsically disordered pathological alpha-synuclein.
资助项目	National Natural Science Foundation of China[21778061] ; National Natural Science Foundation of China[32000890] ; National Natural Science Foundation of China[21977105]
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000638737600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295221]
专题	中国科学院上海药物研究所
通讯作者	Zhou, Chen; Feng, Linyin; Zhang, Naixia
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Analyt Res Ctr Organ & Biol Mol, 555 Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Adv Res Inst, ZhangJiang Lab, Natl Facil Prot Sci Shanghai, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Hu, Huifang,Wang, Qing,Du, Jingwen,et al. Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity[J]. MOLECULES,2021,26(7):20.
APA	Hu, Huifang.,Wang, Qing.,Du, Jingwen.,Liu, Zhijun.,Ding, Yiluan.,...&Zhang, Naixia.(2021).Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity.MOLECULES,26(7),20.
MLA	Hu, Huifang,et al."Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity".MOLECULES 26.7(2021):20.