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DOI	10.1073/pnas.2022269118
	Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins
	Cui W.; Braun E.; Wang W.; Tang J.; Zheng Y.; Slater B.; Li N.; Chen C.; Liu Q.; Wang B.; Li X.; Duan Y.; Xiao Y.; Ti R.; Hotter D.; Ji X.; Zhang L.; Cui J.; Xiong Y.; Sauter D.; Wang Z.; Kirchhoff F.; Yang H.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP51-486), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP51-486 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antiviral factors; Furin inhibition; GTP-induced dimerization; Guanylate-binding proteins; Innate immunity
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179866
作者单位	School of Life Sciences, Tianjin University, Tianjin, 300072, China; Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China; Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China; Institute of Molecular Virology, Ulm University Medical Center, Ulm, 89081, Germany; Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, United States; National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Shanghai, 201210, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, Nanjing, 210023, China; Institute for Medical Virology and Epidemiol...
推荐引用方式 GB/T 7714	Cui W.,Braun E.,Wang W.,et al. Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins[J],2021,118(15).
APA	Cui W..,Braun E..,Wang W..,Tang J..,Zheng Y..,...&Yang H..(2021).Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Cui W.,et al."Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).