The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core Complex
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Coronavirus entry is mediated by the viral spike (S) glycoprotein. The 180-kDa oligomeric S protein of the murine coronavirus mouse hepatitis virus strain A59 is posttranslationally cleaved into an S1 receptor binding unit and an S2 membrane fusion unit. The latter is thought to contain an internal fusion peptide and has two 4,3 hydrophobic (heptad) repeat regions designated HR1 and HR2. HR2 is located close to the membrane anchor, and HR1 is some 170 amino acids (aa) upstream of it. Heptad repeat (HR) regions are found in fusion proteins of many different viruses and form an important characteristic of class I viral fusion proteins. We investigated the role of these regions in coronavirus membrane fusion. Peptides HR1 (96 aa) and HR2 (39 aa), corresponding to the HR1 and HR2 regions, were produced in Escherichia coli. When mixed together, the two peptides were found to assemble into an extremely stable oligomeric complex. Both on their own and within the complex, the peptides were highly alpha helical. Electron microscopic analysis of the complex revealed a rod-like structure approximately 14.5 nm in length. Limited proteolysis in combination with mass spectrometry indicated that HR1 and HR2 occur in the complex in an antiparallel fashion. In the native protein, such a conformation would bring the proposed fusion peptide, located in the N-terminal domain of HR1, and the transmembrane anchor into close proximity. Using biological assays, the HR2 peptide was shown to be a pote…
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Before host cell contact, spike is in a metastable pre-fusion trimer that rearranges substantially during virus-cell fusion.
“Prior to contact with the host cell, the S protein is in a metastable pre-fusion conformation and the trimer undergoes substantial rearrangement at the time of virus–cell fusion150,151.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [151]
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- Authors
- Bosch, B. J., van der Zee, R., de Haan, C. A. M., & Rottier, P. J. M.
- Affiliations
- Utrecht University (NL)
- Immunology Division, Department of Infectious Diseases and Immunity, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands
- Virology Division
- Corresponding author
- Rottier, Peter J. M.
- ORCID
- Bosch, Berend Jan
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2003-08-15
- Volume
- 77
- Issue
- 16
- Pages
- 8801-8811
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC167208
- OpenAlex
- W2097188280
- Cited by
- 1,489
- References
- 1
- Citations by year
- 2026: 25 · 2025: 46 · 2024: 73 · 2023: 104 · 2022: 165 · 2021: 293 · 2020: 342 · 2019: 31 · 2018: 25 · 2017: 27 · 2016: 27 · 2015: 28 · 2014: 35 · 2013: 17 · 2012: 15
- FWCI
- 27.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- coronavirus spike protein, membrane fusion, fusion peptide, mouse hepatitis virus A59, viral entry inhibition, cell-cell fusion inhibition, peptide oligomerization
- MeSH terms
- Amino Acid Sequence, Base Sequence, Circular Dichroism, Membrane Fusion, Membrane Glycoproteins, Microscopy, Electron, Molecular Sequence Data, Viral Envelope Proteins, Sequence Homology, Amino Acid, DNA Primers, Coronavirus, Spike Glycoprotein, Coronavirus
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