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Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein
Christine Toelzer; Kapil Gupta; Sathish KN Yadav; Ufuk Borucu; Frederic Garzoni; Oskar Staufer; Julien Capin; Joachim Spatz; Daniel Fitzgerald; Imre Berger; Christiane Schaffitzel.
Afiliación
  • Christine Toelzer; School of Biochemistry, University of Bristol, 1 Tankards Close, Bristol BS8 1TD, UK.
  • Kapil Gupta; School of Biochemistry, University of Bristol, 1 Tankards Close, Bristol BS8 1TD, UK.
  • Sathish KN Yadav; School of Biochemistry, University of Bristol, 1 Tankards Close, Bristol BS8 1TD, UK.
  • Ufuk Borucu; School of Biochemistry, University of Bristol, 1 Tankards Close, Bristol BS8 1TD, UK.
  • Frederic Garzoni; Imophoron Ltd, St. Philips Central, Albert Rd, St. Philips, Bristol, BS2 0XJ, UK.
  • Oskar Staufer; Department for Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
  • Julien Capin; Bristol Synthetic Biology Centre BrisSynBio, 24 Tyndall Ave, Bristol BS8 1TQ, UK.
  • Joachim Spatz; Department for Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
  • Daniel Fitzgerald; Geneva Biotech Avenue de la Roseraie 64 1205 Geneva Switzerland
  • Imre Berger; Max Planck Bristol Centre for Minimal Biology, Cantock Close, Bristol BS8 1TS, UK
  • Christiane Schaffitzel; School of Biochemistry, University of Bristol, 1 Tankards Close, Bristol BS8 1TD, UK.
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-158584
ABSTRACT
COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly and specifically bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Lipid metabolome remodeling is a key feature of coronavirus infection, with LA at its core. LA metabolic pathways are central to inflammation, immune modulation and membrane fluidity. Our structure directly links LA and S, setting the stage for interventions targeting LA binding and metabolic remodeling by SARS-CoV-2. One Sentence SummaryA direct structural link between SARS-CoV-2 spike and linoleic acid, a key molecule in inflammation, immune modulation and membrane fluidity.
Licencia
cc_by_nc_nd
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2020 Tipo del documento: Preprint