Effects of naturally occurring charged mutations on the structure, stability, and binding of the Pin1 WW domain
文献类型：期刊论文
| 作者 | Qiao, Xiaoya3,4; Liu, Ying2; Luo, Liting1; Chen, Lei1; Zhao, Caixian4; Ai, Xuanjun3 |
| 刊名 | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
 |
| 出版日期 | 2017-05-27 |
| 卷号 | 487页码:470-476 |
| 关键词 | Pin1 Ww Domain Naturally Occurring Mutant Charge Mutation Phosphorylated Tau Nmr Spectroscopy Alzheimer's Disease |
| DOI | 10.1016/j.bbrc.2017.04.093 |
| 英文摘要 | Pin1 is a peptidyl-prolyl cis-trans isomerase, whose WW domain specifically recognizes the pSer/Thr-Pro motif. Pin1 is involved in multiple phosphorylation events that regulate the activities of various substrates, and Pin1 deregulation has been reported in various diseases, including cancer and Alzheimer's disease. The WW domain of Pin1 has been used as a small model protein to investigate the folding mechanisms of the beta-sheet structure by studying the effect of mutations or its naturally occurring variants. However, only a few studies have investigated the structure and binding of Pin1 WW mutants. In the present work, two naturally occurring Pint WW variants, namely, G20D and S16R, derived from the cynomolgus monkey and African green monkey, respectively, were selected to investigate the influence of charge mutation on the structure, stability, and binding properties of the Pin1 WW domain. Analysis using a combination of nuclear magnetic resonance (NMR) and chemical shift-based calculations revealed that the G20D and S16R mutants had high structural similarity to the wild-type Pin1 WW domain. However, the presence of a charge mutation significantly decreased the stability of the Pin1 WW domain. Both the wild-type and G20D forms of the Pin1 WW domain utilized a three-site mode to bind to a phosphorylated Tau peptide, pT231, whereas the S16R mutant binds to the pT231 peptide either in a non-specific manner or through a totally different binding mechanism. Correspondingly, the wild-type and two mutant Pin1 WW domains showed different binding affinities to the Tau phosphopeptide. Considering that the WW domain participates in the catalytic activity of the Pin1 isomerase, our study represents a novel approach for studying Pin1 function through the analysis of its naturally occurring mutants. (C) 2017 Elsevier Inc. All rights reserved. |
| 语种 | 英语 |
| WOS记录号 | WOS:000401683700045 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/152298]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan Ctr Magnet Resonance, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China 2.Natl Ctr AIDS STD Control & Prevent, Div Virol & Immunol, Beijing 102206, Peoples R China 3.Chinese Acad Sci, Dalian Inst Chem Phys, Div Energy Res Resources, Natl Lab Clean Energy, 457 Zhongshan Rd, Dalian 116023, Peoples R China 4.Xiangtan Univ, Sch Chem Engn, Xiangtan 411105, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qiao, Xiaoya,Liu, Ying,Luo, Liting,et al. Effects of naturally occurring charged mutations on the structure, stability, and binding of the Pin1 WW domain[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2017,487:470-476. |
| APA | Qiao, Xiaoya,Liu, Ying,Luo, Liting,Chen, Lei,Zhao, Caixian,&Ai, Xuanjun.(2017).Effects of naturally occurring charged mutations on the structure, stability, and binding of the Pin1 WW domain.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,487,470-476. |
| MLA | Qiao, Xiaoya,et al."Effects of naturally occurring charged mutations on the structure, stability, and binding of the Pin1 WW domain".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 487(2017):470-476. |
入库方式： OAI收割
来源：大连化学物理研究所
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