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TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry.
Wang, Haofeng; Liu, Xiaoce; Zhang, Xiang; Zhao, Zhuoqian; Lu, Yuchi; Pu, Dingzhe; Zhang, Zeyang; Chen, Jie; Wang, Yajie; Li, Mengfei; Dong, Xuxue; Duan, Yinkai; He, Yujia; Mao, Qiyu; Guo, Hangtian; Sun, Haoran; Zhou, Yihan; Yang, Qi; Gao, Yan; Yang, Xiuna; Cao, Hongzhi; Guddat, Luke; Sun, Lei; Rao, Zihe; Yang, Haitao.
Affiliation
  • Wang H; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Liu X; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Zhang X; 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.
  • Zhao Z; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China; Lingang Laboratory, Shanghai 200031, China.
  • Lu Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China; Lingang Laboratory, Shanghai 200031, China.
  • Pu D; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China; Guangzhou Laboratory, Guangzhou 510005, China.
  • Zhang Z; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China; Lingang Laboratory, Shanghai 200031, China.
  • Chen J; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Wang Y; 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.
  • Li M; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Dong X; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China; Guangzhou Laboratory, Guangzhou 510005, China.
  • Duan Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • He Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Mao Q; 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.
  • Guo H; The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
  • Sun H; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Zhou Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Yang Q; Guangzhou Laboratory, Guangzhou 510005, China.
  • Gao Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Yang X; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
  • Cao H; 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.
  • Guddat L; School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
  • Sun L; 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. Electronic address: llsun@fudan.edu.cn.
  • Rao Z; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China; Shanghai Fifth People's Hospital, Shanghai Institute of Infectious Disease and Biose
  • Yang H; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China. Electronic address: yanght@shanghaitech.edu.cn.
Cell ; 2024 Jun 21.
Article in En | MEDLINE | ID: mdl-38964329
ABSTRACT
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Document type: Article Affiliation country: China
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Add to My VHL
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Document type: Article Affiliation country: China