Structural basis for GTP-induced dimerization and antiviral functioin of guanylate-binding proteins

doi:10.1073/pnas.2022269118

	Structural basis for GTP-induced dimerization and antiviral functioin of guanylate-binding proteins
	Cui,Wen 1,2,3; Braun,Elisabeth 4; Wang,Wei 3; Tang,Jinhong 1; Zheng,Yanyan 5; Slater,Benjamin 6; Li,Na 7; Chen,Cheng 1; Liu,Qingxiang 5; Wang,Bin 1; Li,Xiu 1; Duan,Yinkai2 ; Xiao,Yunjie 1; Ti,Rujiao 1; Hotter,Dominik 4; Ji,Xiaoyun 3,8; Zhang,Lei 1; Cui,Jun 5; Xiong,Yong 6; Sauter,Daniel 4,9; Wang,Zefang 1,10; Kirchhoff,Frank 4; Yang,Haitao1,2,10
	2021-04-13
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (IF:9.4[JCR-2023],10.8[5-Year])
ISSN	0027-8424
卷号	118 期号:15
发表状态	已发表
DOI	10.1073/pnas.2022269118
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 GTPloading, 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 HIV1. 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.
关键词	innate immunity guanylate-binding proteins GTP-induced dimerization antiviral factors furin inhibition
收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000641174100006
出版者	NATL ACAD SCIENCES
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125265
专题	生命科学与技术学院_博士生免疫化学研究所_PI研究组_杨海涛组
共同第一作者	Braun,Elisabeth; Wang,Wei; Tang,Jinhong; Zheng,Yanyan
通讯作者	Sauter,Daniel; Wang,Zefang; Kirchhoff,Frank; Yang,Haitao
作者单位	1.School of Life Sciences, Tianjin University, Tianjin, 300072, China 2.Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China 3.Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China 4.Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany 5.Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, 510006 Guangzhou, China 6.Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 7.National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Shanghai, 201204, China 8.State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, Nanjing, 210023, China 9.Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, 72076, Germany 10.Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, 300457, China
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Cui,Wen,Braun,Elisabeth,Wang,Wei,et al. Structural basis for GTP-induced dimerization and antiviral functioin of guanylate-binding proteins[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2021,118(15).
APA	Cui,Wen.,Braun,Elisabeth.,Wang,Wei.,Tang,Jinhong.,Zheng,Yanyan.,...&Yang,Haitao.(2021).Structural basis for GTP-induced dimerization and antiviral functioin of guanylate-binding proteins.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,118(15).
MLA	Cui,Wen,et al."Structural basis for GTP-induced dimerization and antiviral functioin of guanylate-binding proteins".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 118.15(2021).