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-Structure paper
タイトル | Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion. |
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ジャーナル・号・ページ | Cell, Vol. 176, Issue 5, Page 1026-1039.e15, Year 2019 |
掲載日 | 2019年2月21日 |
著者 | Alexandra C Walls / Xiaoli Xiong / Young-Jun Park / M Alejandra Tortorici / Joost Snijder / Joel Quispe / Elisabetta Cameroni / Robin Gopal / Mian Dai / Antonio Lanzavecchia / Maria Zambon / Félix A Rey / Davide Corti / David Veesler / |
PubMed 要旨 | Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways ...Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism. |
リンク | Cell / PubMed:30712865 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.5 - 4.5 Å |
構造データ | EMDB-0401, PDB-6nb3: EMDB-0402, PDB-6nb4: EMDB-0403, PDB-6nb6: EMDB-0404, PDB-6nb7: PDB-6nb5: PDB-6nb8: |
化合物 | ChemComp-NAG: ChemComp-HOH: |
由来 |
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キーワード | VIRUS / coronavirus spike glycoprotein / MERS-CoV / SARS-CoV / human neutralizing antibodies / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / IMMUNE SYSTEM / Fab / Coronavirus / Glycoprotein / SARS |