Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane.

Autor: Shi W; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Cai Y; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; CSL Seqirus, Waltham, MA, USA., Zhu H; Institute for Protein Innovation, Harvard Institutes of Medicine, Boston, MA, USA., Peng H; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Voyer J; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Rits-Volloch S; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Cao H; Codex BioSolutions, Rockville, MD, USA., Mayer ML; The Harvard Cryo-EM Center for Structural Biology, Boston, MA, USA., Song K; Department of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.; Cryo-EM Core Facility, University of Massachusetts Chan Medical School, Worcester, MA, USA., Xu C; Department of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.; Cryo-EM Core Facility, University of Massachusetts Chan Medical School, Worcester, MA, USA., Lu J; Codex BioSolutions, Rockville, MD, USA.; Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC, USA., Zhang J; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. juzhang@crystal.harvard.edu.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. juzhang@crystal.harvard.edu., Chen B; Division of Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. bchen@crystal.harvard.edu.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. bchen@crystal.harvard.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Jul; Vol. 619 (7969), pp. 403-409. Date of Electronic Publication: 2023 Jun 07.
DOI: 10.1038/s41586-023-06273-4
Abstrakt: The entry of SARS-CoV-2 into host cells depends on the refolding of the virus-encoded spike protein from a prefusion conformation, which is metastable after cleavage, to a lower-energy stable postfusion conformation 1,2 . This transition overcomes kinetic barriers for fusion of viral and target cell membranes 3,4 . Here we report a cryogenic electron microscopy (cryo-EM) structure of the intact postfusion spike in a lipid bilayer that represents the single-membrane product of the fusion reaction. The structure provides structural definition of the functionally critical membrane-interacting segments, including the fusion peptide and transmembrane anchor. The internal fusion peptide forms a hairpin-like wedge that spans almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion. These results advance our understanding of the spike protein in a membrane environment and may guide development of intervention strategies.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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