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Solution NMR structure and ligand identification of human Gas7 SH3 domain reveal a typical SH3 fold but a non-canonical ligand-binding mode
Nie, Yao1,2; Zhu, Jiang1; Ramelot, Theresa A.3,4; Kennedy, Michael A.3,4; Liu, Maili1,2; He, Ting1; Yang, Yunhuang1,2
2019-09-03
Source PublicationBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN0006-291X
Volume516Issue:4Pages:1190-1195
AbstractGrowth arrest specific 7 (Gas7) protein is a cytoskeleton regulator playing a crucial role in neural cell development and function, and has been implicated in Alzheimer disease, schizophrenia and cancers. In human, three Gas7 isoforms can be expressed from a single Gas7 gene, while only the longest isoform, hGas7c, possesses an SH3 domain at the N-terminus. To date, the structure and function of hGas7 SH3 domain are still unclear. Here, we reported the solution NMR structure of hGas7 SH3 domain (hGas7-SH3), which displays a typical SH3 beta-barrel fold comprising five beta-strands and one 3(10)-helix. Structural and sequence comparison showed that hGas7-SH3 shares high similarity with Abl SH3 domain, which binds to a high-affinity proline-rich peptide P41 in a canonical SH3-ligand binding mode through two hydrophobic pockets and a specificity site in the RT-loop. However, unlike Abl-SH3, only six residues in the RT-loop and two residues adjacent to but not in the two hydrophobic pockets of hGas7-SH3 showed significant chemical shift perturbations in NMR titrations, suggesting a low affinity and a non canonical binding mode of hGas7-SH3 for P41. Furthermore, four peptides selected from phage-displayed libraries also bound weakly to hGas7-SH3, and the binding region of hGas7-SH3 was mainly located in the RT-loop as well. The ligand identifications through structural similarity searching and peptide library screening in this study imply that although hGas7-SH3 adopts a typical SH3 fold, it probably possesses distinctive ligand-binding specificity. (C) 2019 Elsevier Inc. All rights reserved.
KeywordGrowth arrest specific 7 Src homology 3 NMR structure Praline-rich Phage display
Funding OrganizationNational Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA
DOI10.1016/j.bbrc.2019.07.004
WOS KeywordPROTEIN ; ACTIN ; CONSERVATION ; FAMILY ; CELLS
Language英语
Funding ProjectNational Key R&D Program of China[2016YFA051201] ; National Natural Science Foundation of China[21575155] ; National Institute of General Medical Sciences of USA[U54-GM094597]
Funding OrganizationNational Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institute of General Medical Sciences of USA ; National Institute of General Medical Sciences of USA
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics
WOS SubjectBiochemistry & Molecular Biology ; Biophysics
WOS IDWOS:000479021300021
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
Citation statistics
Document Type期刊论文
Identifierhttp://ir.wipm.ac.cn/handle/112942/14823
Collection中国科学院武汉物理与数学研究所
Corresponding AuthorHe, Ting; Yang, Yunhuang
Affiliation1.Chinese Acad Sci, State Key Lab Magnet Resonance & Atom Mol Phys, Key Lab Magnet Resonance Biol Syst,Natl Ctr Magne, Wuhan Natl Lab Optoelect,Wuhan Inst Phys & Math, Wuhan 430071, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Miami Univ, Dept Chem & Biochem, Oxford, OH 45056 USA
4.Miami Univ, Northeast Struct Genom Consortium, Oxford, OH 45056 USA
Recommended Citation
GB/T 7714
Nie, Yao,Zhu, Jiang,Ramelot, Theresa A.,et al. Solution NMR structure and ligand identification of human Gas7 SH3 domain reveal a typical SH3 fold but a non-canonical ligand-binding mode[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2019,516(4):1190-1195.
APA Nie, Yao.,Zhu, Jiang.,Ramelot, Theresa A..,Kennedy, Michael A..,Liu, Maili.,...&Yang, Yunhuang.(2019).Solution NMR structure and ligand identification of human Gas7 SH3 domain reveal a typical SH3 fold but a non-canonical ligand-binding mode.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,516(4),1190-1195.
MLA Nie, Yao,et al."Solution NMR structure and ligand identification of human Gas7 SH3 domain reveal a typical SH3 fold but a non-canonical ligand-binding mode".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 516.4(2019):1190-1195.
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