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Structure paper

タイトル	Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
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	0401 6nb3 EMDB-0401, PDB-6nb3: MERS-CoV complex with human neutralizing LCA60 antibody Fab fragment (state 1) 手法: EM (単粒子) / 解像度: 3.5 Å 0402 6nb4 EMDB-0402, PDB-6nb4: MERS-CoV S complex with human neutralizing LCA60 antibody Fab fragment (state 2) 手法: EM (単粒子) / 解像度: 3.6 Å 0403 6nb6 EMDB-0403, PDB-6nb6: SARS-CoV complex with human neutralizing S230 antibody Fab fragment (state 1) 手法: EM (単粒子) / 解像度: 4.2 Å 0404 6nb7 EMDB-0404, PDB-6nb7: SARS-CoV complex with human neutralizing S230 antibody Fab fragment (state 2) 手法: EM (単粒子) / 解像度: 4.5 Å PDB-6nb5: Crystal structure of anti- MERS-CoV human neutralizing LCA60 antibody Fab fragment 手法: X-RAY DIFFRACTION / 解像度: 3.0 Å PDB-6nb8: Crystal structure of anti- SARS-CoV human neutralizing S230 antibody Fab fragment 手法: X-RAY DIFFRACTION / 解像度: 1.5 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-HOH: WATER / 水
由来	middle east respiratory syndrome coronavirus (MERSコロナウイルス) middle east respiratory syndrome-related coronavirus (MERSコロナウイルス) homo sapiens (ヒト) sars coronavirus (SARS コロナウイルス)
キーワード	VIRUS (ウイルス) / coronavirus spike glycoprotein / MERS-CoV (MERSコロナウイルス) / SARS-CoV (SARSコロナウイルス) / human neutralizing antibodies (中和抗体) / Structural Genomics (構造ゲノミクス) / Seattle Structural Genomics Center for Infectious Disease / SSGCID / IMMUNE SYSTEM (免疫系) / Fab / Coronavirus (オルトコロナウイルス亜科) / Glycoprotein (糖タンパク質) / SARS (重症急性呼吸器症候群)