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TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry
2024-07-03
发表期刊CELL (IF:45.5[JCR-2023],49.0[5-Year])
ISSN0092-8674
EISSN1097-4172
卷号187期号:16
发表状态已发表
DOI10.1016/j.cell.2024.06.016
摘要The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown. Here, we investigated the HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchored states, revealing that sialoglycan binding induces a conformational change of the NTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition, exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1 features an insertion subdomain that recognizes TMPRSS2 through three previously undiscovered interfaces. Furthermore, structural investigation of HCoV-HKU1A in combination with mutagenesis and binding assays confirms a conserved receptor recognition pattern adopted by HCoV-HKU1. These studies advance our understanding of the complex viral-host interactions during entry, laying the groundwork for developing new therapeutics against coronavirus-associated diseases.
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收录类别SCI
语种英语
资助项目Guangzhou Laboratory["SRPG22-003","SRPG22-011"] ; National Natural Science Foundation of China[92169109] ; Ministry of Science and Technology of the People's Republic of China[2021YFC2302500] ; Science and Technology Commission of Shanghai Municipality[YDZX20213100001556] ; Shanghai Municipal Science and Technology Major Project[ZD2021CY001]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
WOS类目Biochemistry & Molecular Biology ; Cell Biology
WOS记录号WOS:001303129900001
出版者CELL PRESS
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/396015
专题免疫化学研究所_PI研究组_杨海涛组
免疫化学研究所_特聘教授组_饶子和组
生命科学与技术学院_硕士生
生命科学与技术学院_博士生
生命科学与技术学院_本科生
共同第一作者Xiaoce Liu; Xiang Zhang; Zhuoqian Zhao; Yuchi Lu
通讯作者Lei Sun; Zihe Rao; Haitao Yang
作者单位
1.Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
2.Shanghai Clinical Research and Trial Center, Shanghai 201210, China
3.Shanghai Fifth People’s Hospital, Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Key Laboratory of Medical Epigenetics and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
4.Lingang Laboratory, Shanghai 200031, China
5.Guangzhou Laboratory, Guangzhou 510005, China
6.The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China
7.Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
8.School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia
9.Laboratory of Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China
10.State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences and College of Pharmacy, Nankai University, Tianjin 300353, China
11.National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, 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
第一作者的第一单位免疫化学研究所
推荐引用方式
GB/T 7714
Haofeng Wang,Xiaoce Liu,Xiang Zhang,et al. TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry[J]. CELL,2024,187(16).
APA Haofeng Wang.,Xiaoce Liu.,Xiang Zhang.,Zhuoqian Zhao.,Yuchi Lu.,...&Haitao Yang.(2024).TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry.CELL,187(16).
MLA Haofeng Wang,et al."TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry".CELL 187.16(2024).
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