دورية أكاديمية
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, WA, USA., Park YJ; Department of Biochemistry, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA., Stewart C; Department of Biochemistry, University of Washington, Seattle, WA, USA., Sprouse KR; Department of Biochemistry, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA., Addetia A; Department of Biochemistry, University of Washington, Seattle, WA, USA., Brown J; Department of Biochemistry, University of Washington, Seattle, WA, USA., Tortorici MA; Department of Biochemistry, University of Washington, Seattle, WA, USA., Gibson C; Department of Biochemistry, University of Washington, Seattle, WA, 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, WA, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu. |
| المصدر: | Cell [Cell] 2024 Jun 26. Date of Electronic Publication: 2024 Jun 26. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, Ma : Cell Press Original Publication: Cambridge, MIT Press. |
| 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. 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 orthologous proteases. We identified TMPRSS2 orthologs from five mammalian orders promoting HKU1 S-mediated entry into cells along with key residues governing host receptor usage. Our data show that the TMPRSS2 binding motif is a site of vulnerability to neutralizing antibodies and suggest that HKU1 uses S conformational masking and glycan shielding to balance immune evasion and receptor engagement. Competing Interests: Declaration of 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. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Update of: bioRxiv. 2024 Jan 09:2024.01.09.574565. doi: 10.1101/2024.01.09.574565. (PMID: 38260518) |
| فهرسة مساهمة: | Keywords: HKU1; TMPRSS2; coronaviruses; glycan shielding; immune evasion; neutralizing antibodies; species tropism; spike glycoprotein |
| تواريخ الأحداث: | Date Created: 20240704 Latest Revision: 20240715 |
| رمز التحديث: | 20240715 |
| DOI: | 10.1016/j.cell.2024.06.006 |
| PMID: | 38964328 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4172 |
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| DOI: | 10.1016/j.cell.2024.06.006 |