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

doi:10.1126/science.abd3255

GSTDTAP > 气候变化

DOI	10.1126/science.abd3255
	Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein
	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
	2020-11-06
发表期刊	Science
出版年	2020
英文摘要	Many efforts to develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the spike (S) protein trimer that binds to the host receptor. Structures of trimeric S protein show its receptor-binding domain in either an up or a down conformation. Toelzer et al. produced SARS-CoV-2 S in insect cells and determined the structure by cryo–electron microscopy. In their dataset, the closed form was predominant and was stabilized by binding linoleic acid, an essential fatty acid. A similar binding pocket appears to be present in previous highly pathogenic coronaviruses, and past studies suggested links between viral infection and fatty acid metabolism. The pocket could be exploited to develop inhibitors that trap S protein in the closed conformation. Science , this issue p. [725][1] 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. [1]: /lookup/doi/10.1126/science.abd3255
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/302005
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Christine Toelzer,Kapil Gupta,Sathish K. N. Yadav,et al. Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein[J]. Science,2020.
APA	Christine Toelzer.,Kapil Gupta.,Sathish K. N. Yadav.,Ufuk Borucu.,Andrew D. Davidson.,...&Christiane Schaffitzel.(2020).Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein.Science.
MLA	Christine Toelzer,et al."Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein".Science (2020).