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研究发现SARS-CoV-2突刺蛋白中的游离脂肪酸结合口袋
作者:小柯机器人 发布时间:2020/9/24 12:52:25

英国布里斯托大学Christiane Schaffitzel、Imre Berger等研究人员合作发现SARS-CoV-2突刺蛋白中的游离脂肪酸结合口袋。相关论文于2020年9月21日在线发表于国际学术期刊《科学》。

研究人员报道了分辨率为2.85Å的SARS-CoV-2突刺糖蛋白(S)的冷冻电镜结构,从而揭示了受体结合域(RBD)可紧密结合必需的游离脂肪酸(FFA)亚油酸(LA)。高致病性冠状病毒SARS-CoV和MERS-CoV中也似乎存在该口袋。LA结合可稳定锁定的S构象,从而在体外降低ACE2的相互作用。在人类细胞中,LA补充剂能够与COVID-19药物瑞德西韦协同作用,从而抑制SARS-CoV-2复制。
 
这一结构直接联系了LA和S,从而为靶向SARS-CoV-2与LA结合的干预策略奠定了基础。
 
据介绍,SARS-CoV-2引起的COVID-19是全球性危机。SARS-CoV-2疗法开发的关键是揭示导致高感染性、广泛组织嗜性和严重病理背后的机制。
 
附:英文原文

Title: Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein

Author: 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

Issue&Volume: 2020/09/21

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 2.85 cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly 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. LA binding stabilizes a locked S conformation giving rise to reduced 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 targeting LA binding by SARS-CoV-2.

DOI: 10.1126/science.abd3255

Source: https://science.sciencemag.org/content/early/2020/09/18/science.abd3255

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037