Human Aha1's N-terminal extension confers it holdase activity in vitro
文献类型：期刊论文
| 作者 | Tang, Junying1,2; Hu, Huifang2,3; Zhou, Chen2,4; Zhang, Naixia1,2,3,4
|
| 刊名 | PROTEIN SCIENCE
 |
| 出版日期 | 2023-09-01 |
| 卷号 | 32期号:9页码:15 |
| ISSN号 | 0961-8368 |
| 关键词 | Aha1 holdase activity intrinsically disordered region NMR N-terminal extension |
| DOI | 10.1002/pro.4735 |
| 通讯作者 | Zhou, Chen(czhou@simm.ac.cn) ; Zhang, Naixia(nxzhang@simm.ac.cn) |
| 英文摘要 | Molecular chaperones are key components of protein quality control system, which plays an essential role in controlling protein homeostasis. Aha1 has been identified as a co-chaperone of Hsp90 known to strongly accelerate Hsp90's ATPase activity. Meanwhile, it is reported that Aha1 could also act as an autonomous chaperone and protect stressed or disordered proteins from aggregation. Here, in this article, a series of in vitro experiments were conducted to verify whether Aha1 has a non-Hsp90-dependent holdase activity and to elucidate the associated molecular mechanism for substrate recognition. According to the results of the refolding assay, the highly conserved N-terminal extension spanning M1 to R16 in Aha1 from higher eukaryotes is responsible for the holdase activity of the protein. As revealed by the NMR data, Aha1's N-terminal extension mainly adopts a disordered conformation in solution and shows no tight contacts with the core structure of Aha1's N-terminal domain. Based on the intrinsically disordered structure feature and the primary sequence of Aha1's N-terminal extension, the fuzzy-type protein-protein interactions involving this specific region and the unfolded substrate proteins are expected. The following mutation analysis data demonstrated that the Van der Waals contacts potentially involving two tryptophans including W4 and W11 do not play a dominant role in the interaction between Aha1 and unfolded maltose binding protein (MBP). Meanwhile, since the high concentration of NaCl could abolish the holdase activity of Aha1, the electrostatic interactions mediated by those charged residues in Aha1's N-terminal extension are thus indicated to play a crucial role in the substrate recognition. |
| WOS关键词 | MOLECULAR CHAPERONES ; AUTONOMOUS CHAPERONE ; HSP90 ; ACTIVATION ; MECHANISM |
| 资助项目 | National Natural Science Foundation of China[32171220] ; National Natural Science Foundation of China[22107111] ; National Natural Science Foundation of China[21977105] ; Shanghai Municipal Science and Technology Major Project ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2022284] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:001052467000001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306977]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhou, Chen; Zhang, Naixia |
| 作者单位 | 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 2.Chinese Acad Sci, State Key Lab Chem Biol, Analyt Res Ctr Organ & Biol Mol, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Chinese Acad Sci, State Key Lab Chem Biol, Analyt Res Ctr Organ & Biol Mol, Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tang, Junying,Hu, Huifang,Zhou, Chen,et al. Human Aha1's N-terminal extension confers it holdase activity in vitro[J]. PROTEIN SCIENCE,2023,32(9):15. |
| APA | Tang, Junying,Hu, Huifang,Zhou, Chen,&Zhang, Naixia.(2023).Human Aha1's N-terminal extension confers it holdase activity in vitro.PROTEIN SCIENCE,32(9),15. |
| MLA | Tang, Junying,et al."Human Aha1's N-terminal extension confers it holdase activity in vitro".PROTEIN SCIENCE 32.9(2023):15. |
入库方式： OAI收割
来源：上海药物研究所
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