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Nanobodies and chemical cross-links advance the structural and functional analysis of PI3K alpha

文献类型：期刊论文

作者Hart, Jonathan R.1; Liu, Xiao2,3; Pan, Chen4; Liang, Anyi5; Ueno, Lynn; Xu, Yingna6; Quezada, Alexandra1; Zou, Xinyu5; Yang, Su1; Zhou, Qingtong6
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2022-09-20
卷号119期号:38页码:9
ISSN号0027-8424
关键词phosphoinositide 3-kinase (PI3K) nanobody conformational changes chemical cross-linking mass spectrometry
DOI10.1073/pnas.2210769119
通讯作者Shui, Wenqing(shuiwq@shanghaitech.edu.cn) ; Yang, Dehua(dhyang@simm.ac.cn) ; Vogt, Peter K.(pkvogt@scripps.edu) ; Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要Nanobodies and chemical cross-linking were used to gain information on the identity and positions of flexible domains of PI3K alpha. The application of chemical cross-linking mass spectrometry (CXMS) facilitated the identification of the p85 domains BH, cSH2, and SH3 as well as their docking positions on the PI3K alpha catalytic core. Binding of individual nanobodies to PI3K alpha induced activation or inhibition of enzyme activity and caused conformational changes that could be correlated with enzyme function. Binding of nanobody Nb3-126 to the BH domain of p85a substantially improved resolution for parts of the PI3K alpha complex, and binding of nanobody Nb3-159 induced a conformation of PI3K alpha that is distinct from known PI3K alpha structures. The analysis of CXMS data also provided mechanistic insights into the molecular underpinning of the flexibility of PI3K alpha.
WOS关键词P85-ALPHA REGULATORY SUBUNIT ; SH2 DOMAIN ; PI3K ; ACTIVATION ; INHIBITOR ; MUTATIONS ; 3-KINASE ; CANCER ; LYMPHOMA ; FEATURES
资助项目National Cancer Institute[R35 CA197582] ; National Cancer Institute[R50 CA243899] ; National Cancer Institute[30186] ; National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[31971362] ; National Natural Science Foundation of China[32171439] ; National Natural Science Foundation of China[21704064] ; National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09735-001] ; National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09711002-002-005] ; National Key Basic Research Program of China[2018YFA0507000] ; Hainan Provincial Major Science and Technology Project[ZDKJ2021028] ; Novo Nordisk-Chinese Academy of Sciences Research Fund[NNCAS-2017-1-CC] ; National Science and Technology Major Project of China-Innovation 2030 for Brain Science and Brain-Inspired Technology[2021ZD0203400]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATL ACAD SCIENCES
WOS记录号WOS:001043065200011
源URL[http://119.78.100.183/handle/2S10ELR8/306950]  
专题中国科学院上海药物研究所
通讯作者Shui, Wenqing; Yang, Dehua; Vogt, Peter K.; Wang, Ming-Wei
作者单位1.Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.ShanghaiTech Univ, iHuman Inst, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
5.Huazhong Univ Sci & Technol, Sch Artificial Intelligence & Automat, Wuhan 430074, Peoples R China
6.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
7.Vrije Univ Brussel, Vlaams Inst Biotechnol, Nanobody Core, B-1050 Brussels, Belgium
8.Res Ctr Deepsea Bioresources, Sanya 572025, Peoples R China
9.Univ Tokyo, Sch Sci, Dept Chem, Tokyo 1130033, Japan
推荐引用方式
GB/T 7714		 Hart, Jonathan R.,Liu, Xiao,Pan, Chen,et al. Nanobodies and chemical cross-links advance the structural and functional analysis of PI3K alpha[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2022,119(38):9.
APA Hart, Jonathan R..,Liu, Xiao.,Pan, Chen.,Liang, Anyi.,Ueno, Lynn.,...&Wang, Ming-Wei.(2022).Nanobodies and chemical cross-links advance the structural and functional analysis of PI3K alpha.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,119(38),9.
MLA Hart, Jonathan R.,et al."Nanobodies and chemical cross-links advance the structural and functional analysis of PI3K alpha".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119.38(2022):9.

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来源：上海药物研究所

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