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与保护性埃博拉病毒抗体结合的粘蛋白域线性表位的结构。

Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus.

机构信息

Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.

出版信息

J Virol. 2012 Mar;86(5):2809-16. doi: 10.1128/JVI.05549-11. Epub 2011 Dec 14.

Abstract

Antibody 14G7 is protective against lethal Ebola virus challenge and recognizes a distinct linear epitope in the prominent mucin-like domain of the Ebola virus glycoprotein GP. The structure of 14G7 in complex with its linear peptide epitope has now been determined to 2.8 Å. The structure shows that this GP sequence forms a tandem β-hairpin structure that binds deeply into a cleft in the antibody-combining site. A key threonine at the apex of one turn is critical for antibody interaction and is conserved among all Ebola viruses. This work provides further insight into the mechanism of protection by antibodies that target the protruding, highly accessible mucin-like domain of Ebola virus and the structural framework for understanding and characterizing candidate immunotherapeutics.

摘要

抗体 14G7 可预防致命的埃博拉病毒感染,能识别埃博拉病毒糖蛋白 GP 中突出的黏液样结构域上的独特线性表位。现在已经确定了 14G7 与其线性肽表位复合物的结构,分辨率为 2.8Å。结构表明,GP 序列形成串联 β-发夹结构,深入结合到抗体结合位点的裂缝中。一个转角顶端的关键苏氨酸对于抗体相互作用至关重要,并且在所有埃博拉病毒中都保守。这项工作进一步深入了解了针对埃博拉病毒突出的高度可及的黏液样结构域的抗体的保护机制,以及理解和表征候选免疫疗法的结构框架。

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