7ZH2

SARS CoV Spike protein, Closed C1 conformation

7ZH2 の概要

• エントリーDOI: 10.2210/pdb7zh2/pdb
• EMDBエントリー: 14718
• 分子名称: Spike glycoprotein,Fibritin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, LINOLEIC ACID, ... (4 entities in total)
• 機能のキーワード: sars-cov, viral protein, spike
• 由来する生物種: Severe acute respiratory syndrome-related coronavirus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 416692.54

構造登録者

Toelzer, C.,Gupta, K.,Yadav, S.K.N.,Buzas, D.,Borucu, U.,Schaffitzel, C.,Berger, I. (登録日: 2022-04-05, 公開日: 2023-02-15, 最終更新日: 2024-11-20)

主引用文献

Toelzer, C.,Gupta, K.,Yadav, S.K.N.,Hodgson, L.,Williamson, M.K.,Buzas, D.,Borucu, U.,Powers, K.,Stenner, R.,Vasileiou, K.,Garzoni, F.,Fitzgerald, D.,Payre, C.,Gautam, G.,Lambeau, G.,Davidson, A.D.,Verkade, P.,Frank, M.,Berger, I.,Schaffitzel, C.
The free fatty acid-binding pocket is a conserved hallmark in pathogenic beta-coronavirus spike proteins from SARS-CoV to Omicron.
Sci Adv, 8:eadc9179-eadc9179, 2022

PubMed Abstract: As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)-binding pocket. FFA binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold-causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation, while the open, infectious conformation is devoid of LA. Electron tomography of SARS-CoV-2-infected cells reveals that LA treatment inhibits viral replication, resulting in fewer deformed virions. Our results establish FFA binding as a hallmark of pathogenic β-CoV infection and replication, setting the stage for FFA-based antiviral strategies to overcome COVID-19.

PubMed: 36417532
DOI: 10.1126/sciadv.adc9179

実験手法

ELECTRON MICROSCOPY (2.71 Å)