Human coronavirus HKU1 recognition of the TMPRSS2 host receptor.
| العنوان: | Human coronavirus HKU1 recognition of the TMPRSS2 host receptor. |
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| المؤلفون: | McCallum M; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Park YJ; Department of Biochemistry, University of Washington, Seattle, Washington, USA.; Howard Hughes Medical Institute, Seattle, WA 98195, USA., Stewart C; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Sprouse KR; Department of Biochemistry, University of Washington, Seattle, Washington, USA.; Howard Hughes Medical Institute, Seattle, WA 98195, USA.; Vir Biotechnology, San Francisco, CA 94158, USA.; Laboratory of Clinical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium., Brown J; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Tortorici MA; Department of Biochemistry, University of Washington, Seattle, Washington, USA., Gibson C; Department of Biochemistry, University of Washington, Seattle, Washington, USA.; Howard Hughes Medical Institute, Seattle, WA 98195, USA., Wong E; Vir Biotechnology, San Francisco, CA 94158, USA., Ieven M; Laboratory of Clinical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium., Telenti A; Vir Biotechnology, San Francisco, CA 94158, USA., Veesler D; Department of Biochemistry, University of Washington, Seattle, Washington, USA.; Howard Hughes Medical Institute, Seattle, WA 98195, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 09. Date of Electronic Publication: 2024 Jan 09. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to TMPRSS2 and determinants of host receptor tropism remain elusive. Here, we designed an active human TMPRSS2 construct enabling high-yield recombinant production in human cells of this key therapeutic target. We determined a cryo-electron microscopy structure of the HKU1 RBD bound to human TMPRSS2 providing a blueprint of the interactions supporting viral entry and explaining the specificity for TMPRSS2 among human type 2 transmembrane serine proteases. We found that human, rat, hamster and camel TMPRSS2 promote HKU1 S-mediated entry into cells and identified key residues governing host receptor usage. Our data show that serum antibodies targeting the HKU1 RBD TMPRSS2 binding-site are key for neutralization and that HKU1 uses conformational masking and glycan shielding to balance immune evasion and receptor engagement. Competing Interests: Competing Interests M.M. and D.V. are named as inventors on a patent describing the designed TMPRSS2 constructs and D.V. is named as inventor on patents for coronavirus vaccines filed by the University of Washington. E.W. and A.T. are employees of Vir Biotechnology and may hold shares in Vir Biotechnology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| التعليقات: | Update in: Cell. 2024 Jun 26:S0092-8674(24)00646-9. doi: 10.1016/j.cell.2024.06.006. (PMID: 38964328) |
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| معلومات مُعتمدة: | 75N93022C00036 United States AI NIAID NIH HHS; DP1 AI158186 United States AI NIAID NIH HHS; P01 AI167966 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20240123 Latest Revision: 20240715 |
| رمز التحديث: | 20240715 |
| مُعرف محوري في PubMed: | PMC10802434 |
| DOI: | 10.1101/2024.01.09.574565 |
| PMID: | 38260518 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2692-8205 |
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| DOI: | 10.1101/2024.01.09.574565 |