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TitleStructure-guided covalent stabilization of coronavirus spike glycoprotein trimers in the closed conformation.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 10, Page 942-949, Year 2020
Publish dateAug 4, 2020
AuthorsMatthew McCallum / Alexandra C Walls / John E Bowen / Davide Corti / David Veesler /
PubMed AbstractSARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein ...SARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface and fusion of the viral and host membranes. Prefusion SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design. However, its limited stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a construct corresponding to the prefusion SARS-CoV-2 S ectodomain trimer, covalently stabilized by a disulfide bond in the closed conformation. Structural and antigenicity analyses show we successfully shut S in the closed state without otherwise altering its architecture. We demonstrate that this strategy is applicable to other β-coronaviruses, such as SARS-CoV and MERS-CoV, and might become an important tool for structural biology, serology, vaccine design and immunology studies.
External linksNat Struct Mol Biol / PubMed:32753755 / PubMed Central
MethodsEM (single particle)
Resolution2.9 Å
Structure data

22083

6x79

EMDB-22083, PDB-6x79:
Prefusion SARS-CoV-2 S ectodomain trimer covalently stabilized in the closed conformation
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / SARS-CoV-2 / COVID-19 / coronavirus spike glycoprotein / fusion protein / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID

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