6ZB4

SARS CoV-2 Spike protein, Closed conformation, C1 symmetry

Summary for 6ZB4

• Entry DOI: 10.2210/pdb6zb4/pdb
• EMDB information: 11144
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov2, covid, viral protein, linoleic acid, spike
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 3
• Total formula weight: 426003.70

Authors

Toelzer, C.,Gupta, K.,Yadav, S.K.N.,Burucu, U.,Schaffitzel, C.,Berger, I. (deposition date: 2020-06-06, release date: 2020-09-30, Last modification date: 2020-11-18)

Primary citation

Toelzer, C.,Gupta, K.,Yadav, S.K.N.,Borucu, U.,Davidson, A.D.,Kavanagh Williamson, M.,Shoemark, D.K.,Garzoni, F.,Staufer, O.,Milligan, R.,Capin, J.,Mulholland, A.J.,Spatz, J.,Fitzgerald, D.,Berger, I.,Schaffitzel, C.
Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein.
Science, 370:725-730, 2020

PubMed Abstract: Coronavirus disease 2019 (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 that drive high infectivity, broad tissue tropism, and severe pathology. Our 2.85-angstrom cryo-electron microscopy structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains tightly bind the essential free fatty acid linoleic acid (LA) in three composite binding pockets. A similar pocket also appears to be present in the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). LA binding stabilizes a locked S conformation, resulting in reduced angiotensin-converting enzyme 2 (ACE2) interaction in vitro In human cells, LA supplementation synergizes with the COVID-19 drug remdesivir, suppressing SARS-CoV-2 replication. Our structure directly links LA and S, setting the stage for intervention strategies that target LA binding by SARS-CoV-2.

PubMed: 32958580
DOI: 10.1126/science.abd3255

Experimental method

ELECTRON MICROSCOPY (3.03 Å)