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| DOI | 10.1126/science.abd3255 |
| Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein | |
| Toelzer C.; Gupta K.; Yadav S.K.N.; Borucu U.; Davidson A.D.; Williamson M.K.; Shoemark D.K.; Garzoni F.; Staufer O.; Milligan R.; Capin J.; Mulholland A.J.; Spatz J.; Fitzgerald D.; Berger I.; Schaffitzel C. | |
| 发表日期 | 2020 |
| ISSN | 0036-8075 |
| 起始页码 | 725 |
| 结束页码 | 730 |
| 卷号 | 370期号:6517 |
| 英文摘要 | 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. © 2020 American Association for the Advancement of Science. All rights reserved. |
| 英文关键词 | angiotensin converting enzyme 2; coronavirus spike glycoprotein; linoleic acid; remdesivir; angiotensin converting enzyme 2; coronavirus spike glycoprotein; dipeptidyl carboxypeptidase; linoleic acid; spike protein, SARS-CoV-2; fatty acid; infectivity; pathogenicity; protein; respiratory disease; viral disease; animal cell; Article; controlled study; cryoelectron microscopy; HEK293 cell line; human; human cell; insect cell; nonhuman; priority journal; protein conformation; protein interaction; protein structure; Severe acute respiratory syndrome coronavirus 2; virus inhibition; amino acid sequence; animal; Betacoronavirus; binding site; chemistry; Chlorocebus aethiops; metabolism; Middle East respiratory syndrome coronavirus; molecular model; protein domain; protein tertiary structure; SARS coronavirus; ultrastructure; Vero cell line; Middle East; Coronavirus; SARS coronavirus; Amino Acid Sequence; Animals; Betacoronavirus; Binding Sites; Chlorocebus aethiops; Cryoelectron Microscopy; Humans; Linoleic Acid; Middle East Respiratory Syndrome Coronavirus; Models, Molecular; Peptidyl-Dipeptidase A; Protein Interaction Domains and Motifs; Protein Structure, Tertiary; SARS Virus; Spike Glycoprotein, Coronavirus; Vero Cells |
| 语种 | 英语 |
| 来源期刊 | Science
 |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/245761 |
| 作者单位 | School of Biochemistry, University of Bristol, 1 Tankard’s Close, Bristol, BS8 1TD, United Kingdom; Bristol Synthetic Biology Centre BrisSynBio, 24 Tyndall Ave., Bristol, BS8 1TQ, United Kingdom; School of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol, BS8 1TD, United Kingdom; Imophoron Ltd., St. Philips Central, Albert Rd., St. Philips, Bristol, BS2 0XJ, United Kingdom; Department for Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstraße 29, Heidelberg, 69120, Germany; Institute for Physical Chemistry, Department for Biophysical Chemistry, University of Heidelberg, Im Neuenheimer Feld 253, Heidelberg, 69120, Germany; Max Planck School Matter to Life, Jahnstraße 29, Heidelberg, D-69120, Germany; Max Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol, BS8 1TS, United Kingdom; School of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom; Geneva Biotech Sàrl, Avenue de la Roseraie 64, Geneva, 1205, Switz... |
| 推荐引用方式 GB/T 7714 | Toelzer C.,Gupta K.,Yadav S.K.N.,et al. Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein[J],2020,370(6517). |
| APA | Toelzer C..,Gupta K..,Yadav S.K.N..,Borucu U..,Davidson A.D..,...&Schaffitzel C..(2020).Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein.Science,370(6517). |
| MLA | Toelzer C.,et al."Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein".Science 370.6517(2020). |
| 条目包含的文件 | 条目无相关文件。 | |||||
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