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-Structure paper
タイトル | Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD. |
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ジャーナル・号・ページ | Cell Rep, Vol. 28, Issue 13, Page 3395-33405.e6, Year 2019 |
掲載日 | 2019年9月24日 |
著者 | Nianshuang Wang / Osnat Rosen / Lingshu Wang / Hannah L Turner / Laura J Stevens / Kizzmekia S Corbett / Charles A Bowman / Jesper Pallesen / Wei Shi / Yi Zhang / Kwanyee Leung / Robert N Kirchdoerfer / Michelle M Becker / Mark R Denison / James D Chappell / Andrew B Ward / Barney S Graham / Jason S McLellan / |
PubMed 要旨 | Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the ...Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV. |
リンク | Cell Rep / PubMed:31553909 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.1 - 24.0 Å |
構造データ | EMDB-0486: EMDB-20527: MERS S0 trimer in complex with antibody G2 PDB-6pxg: PDB-6pxh: |
化合物 | ChemComp-HOH: ChemComp-NAG: ChemComp-SO4: ChemComp-DHF: |
由来 |
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キーワード | IMMUNE SYSTEM / antibody / fusion glycoprotein / IMMUNE SYSTEM/Viral protein / IMMUNE SYSTEM-Viral protein complex / VIRAL PROTEIN/IMMUNE SYSTEM / MERS-CoV / coronavirus / DPP4 / receptor-binding / membrane fusion / VIRAL PROTEIN-IMMUNE SYSTEM complex |