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首页> 外文期刊>Journal of Molecular Biology >CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody–Antigen Interface
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CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody–Antigen Interface

机译：流感病毒受体结合位点抗体 - 抗原界面的Cryoem结构

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Abstract Structure-based vaccine design depends on extensive structural analyses of antigen–antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can circumvent some of the problems of x-ray crystallography as a pipeline for obtaining the required structures. We have examined the potential of single-particle cryoEM for determining the structure of influenza-virus hemagglutinin (HA):single-chain variable-domain fragment complexes, by studying a complex we failed to crystallize in pursuing an extended project on the human immune response to influenza vaccines.The result shows that a combination of cryoEM and molecular modeling can yield details of the antigen-antibody interface, although small variation in the twist of the rod-likeHA trimer limited the overall resolution to about 4.5 ?.Comparison of principal 3D classes suggests ways to modify the HA trimer to overcome this limitation. A closely related antibody from the same donor did yield crystals when bound with the same HA, giving us an independent validation of the cryoEM results.The two structures also augment our understanding of receptor-binding site recognition by antibodies that neutralize a wide range of influenza-virus variants. Graphical Abstract Display Omitted Highlights ? Single-particle cryoEM of antigen–antibody complexes ? Influenza virus HA bound with single-chain Fv ? cryoEM and molecular modeling yield details of the antigen:antibody interface. ? HA receptor-binding site recognition by broadly neutralizing antibodies
机译：摘要基于结构的疫苗设计取决于抗原 - 抗体复合物的广泛结构分析。粒子电子冷冻镜（Cryoem）可以绕过X射线晶体学的一些问题作为获得所需结构的管道。我们研究了单粒子低温的潜力，用于确定流感病毒血凝素（HA）的结构：单链可变域片段复合物，通过研究复杂，我们未能结晶，以追求人类免疫反应的扩展项目结果表明，Cryoem和分子建模的组合可以产生抗原 - 抗体界面的细节，但棒状三聚体扭曲的小变化限制了大约4.5的总分辨率为约4.5°Comparison课程表明如何修改HA修剪以克服此限制。与同一供体的密切相关的抗体在用相同的HA结合时屈服晶体，使我们对Cryoem结果的独立验证。这两个结构也通过中和各种流感的抗体来增加对受体结合位点识别的理解-virus变体。图形抽象显示省略了亮点？抗原 - 抗体复合物的单粒子Cryoem？流感病毒HA与单链Fv结合？ Cryoem和分子建模的抗原的细节：抗体界面。还是HA受体结合的位点通过广泛中和抗体识别

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