6ZB4

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

6ZB4 の概要

• エントリーDOI: 10.2210/pdb6zb4/pdb
• EMDBエントリー: 11144
• 分子名称: 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)
• 機能のキーワード: sars-cov2, covid, viral protein, linoleic acid, spike
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 426003.70

構造登録者

Toelzer, C.,Gupta, K.,Yadav, S.K.N.,Burucu, U.,Schaffitzel, C.,Berger, I. (登録日: 2020-06-06, 公開日: 2020-09-30, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.03 Å)