+検索条件
-Structure paper
タイトル | Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein. |
---|---|
ジャーナル・号・ページ | Science, Vol. 370, Issue 6517, Page 725-730, Year 2020 |
掲載日 | 2020年11月6日 |
著者 | Christine Toelzer / Kapil Gupta / Sathish K N Yadav / Ufuk Borucu / Andrew D Davidson / Maia Kavanagh Williamson / Deborah K Shoemark / Frederic Garzoni / Oskar Staufer / Rachel Milligan / Julien Capin / Adrian J Mulholland / Joachim Spatz / Daniel Fitzgerald / Imre Berger / Christiane Schaffitzel / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:32958580 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.85 - 3.55 Å |
構造データ | EMDB-11144, PDB-6zb4: EMDB-11145, PDB-6zb5: EMDB-11146: |
化合物 | ChemComp-NAG: ChemComp-EIC: |
由来 |
|
キーワード | VIRAL PROTEIN / SARS-Cov2 / COVID / Linoleic Acid / Spike |