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Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26

  • [设施]:上海光源
  • [期刊/会议名称]:Nature, 500(7461):227-31(2013-8-8)
  • [摘要]:The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans(1,2), representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV3. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV4. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 beta-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein-protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among beta-coronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition.
  • [发表日期]:2013
  • [第一作者]:Lu, Guangwen
  • [第一作者单位]:中科院微生物所
  • [通讯作者]:高福
  • [通讯作者单位]:中科院微生物所
  • [论文类型]:期刊
  • [期刊分类]:SCI1区
  • [学科分类]:生物学_ 生物化学
  • [影响因子]:
  • [关键词]:RESPIRATORY-SYNDROME CORONAVIRUS; CRYSTAL-STRUCTURE; SPIKE PROTEIN; FUNCTIONAL RECEPTOR; SARS CORONAVIRUS; AMINOPEPTIDASE-N; MIDDLE-EAST; REVEALS; MEMBRANE; COMPLEX
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  • [简介]:随着交通运输水平的提高,流动人口的增加,由各种病原体引起的能在人与人、动物与动物或人与动物之间相互传播的一类疾病的防治与研究显的尤为重要。中国科学院北京生命科学研究院/微生物研究所高福课题组利用上海光源生物大分子晶体学光束线站(BL17U1),在高致病性禽流感感染人传播机制及跨种传播机制和新冠状病毒侵入宿主细胞机制研究等方面开展研究,取得重要进展。