Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor

Basore Katherine; Ma Hongming; Kafai Natasha M.; Mackin Samantha; Kim Arthur S.; Nelson Christopher A.; Diamond Michael S.; Fremont Daved H.

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Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor

机译：委内瑞拉大核脑炎病毒与LDLAD3受体复合物的结构

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LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)(1), a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor type-A module that binds to VEEV by wedging into a cleft created by two adjacent E2-E1 heterodimers in one trimeric spike, and engages domains A and B of E2 and the fusion loop in E1. Atomic modelling of this interface is supported by mutagenesis and anti-VEEV antibody binding competition assays. Notably, VEEV engages LDLRAD3 in a manner that is similar to the way that arthritogenic alphaviruses bind to the structurally unrelated MXRA8 receptor, but with a much smaller interface. These studies further elucidate the structural basis of alphavirus-receptor interactions, which could inform the development of therapies to mitigate infection and disease against multiple members of this family.

机译：LDLRAD3是最近定义的委内瑞拉Qualine脑炎病毒（VEEV）（1）的最近定义的附件和入口受体，这是一种新的世界alphavirous，导致人类严重的神经疾病。在这里，我们将近似原子分辨率冷冻电子显微镜重建单独进行veev病毒样颗粒，并与Ldlrad3的突出部的复合物。 LDLRAD3的域1是低密度脂蛋白受体型-A模块结合VEEV通过楔入到由两个相邻的E2-E1异二聚体，一个三聚体刺突创建的裂口，并且接合结构域A和E2的B和在融合环E1。该界面的原子建模由诱变和抗VEEV抗体结合竞争测定来支持。值得注意的是，VEEV以类似于动力学alphirouses与结构不相关的MXRA8受体结合的方式的方式接合Ldlrad3，但是具有更小的界面。这些研究进一步阐明了甲病毒 - 受体相互作用的结构依据，这可以为疗法提供减轻对这个家庭多个成员的感染和疾病的发展。

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《Nature》 |2021年第7882期|672-676|共5页
作者
Basore Katherine; Ma Hongming; Kafai Natasha M.; Mackin Samantha; Kim Arthur S.; Nelson Christopher A.; Diamond Michael S.; Fremont Daved H.;
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Washington Univ Dept Pathol Immunol Sch Med St Louis MO 14263 USA;

Washington Univ Dept Med Sch Med St Louis MO 14263 USA;

Washington Univ Dept Pathol Immunol Sch Med St Louis MO 14263 USA|Washington Univ Dept Med Sch Med St Louis MO 14263 USA;

Washington Univ Dept Pathol Immunol Sch Med St Louis MO 14263 USA|Washington Univ Dept Med Sch Med St Louis MO 14263 USA;

Washington Univ Dept Pathol Immunol Sch Med St Louis MO 14263 USA;

Washington Univ Dept Pathol Immunol Sch Med St Louis MO 14263 USA;

Washington Univ Dept Pathol Immunol Sch Med St Louis MO 14263 USA|Washington Univ Dept Med Sch Med St Louis MO 14263 USA|Washington Univ Dept Mol Microbiol Sch Med St Louis MO 14263 USA|Washington Univ Andrew M & Jane M Bursky Ctr Human Immunol & Immu Sch Med St Louis MO 14263 USA;

Washington Univ Dept Pathol Immunol Sch Med St Louis MO 14263 USA|Washington Univ Dept Med Sch Med St Louis MO 14263 USA|Washington Univ Dept Mol Microbiol Sch Med St Louis MO 14263 USA|Washington Univ Andrew M & Jane M Bursky Ctr Human Immunol & Immu Sch Med St Louis MO 14263 USA|Washington Univ Dept Biochem Mol Biophys Sch Med St Louis MO 14263 USA;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3 [J] . Ma Bingting, Huang Cuiqing, Ma Jun, Nature . 2021,第7882期

机译：委内瑞拉群体脑膜炎病毒与受体LDLRAD3的结构
2. LDLRAD3 is a receptor for Venezuelan equine encephalitis virus [J] . Ma Hongming, Kim Arthur S., Kafai Natasha M., Nature . 2020,第7837期

机译：LDLRAD3是委内瑞拉大当脑脑炎病毒的受体
3. Possible Evidence for Interference with Venezuelan Equine Encephalitis Virus Vaccination of Equines by Pre-Existing Antibody to Eastern or Western Equine Encephalitis Virus, or Both [J] . Charles H. Calisher, Donna R. Sasso, Gladys E. Sather Applied Microbiology . 1973,第4期

机译：通过东部或西部马脑炎病毒（或两者）既存的抗体干扰委内瑞拉马脑炎病毒的疫苗接种的可能证据
4. Comparative Epidemiologies of Eastern Equine Encephalitis Virus, Western Equine Encephalitis Virus, Venezuelan Equine Encephalitis Virus, and West Nile Virus [C] . Charles H. Calisher Annual Meeting of the American Society for Veterinary Clinical Pathology . 2004

机译：东部大雄脑炎病毒，西马脑炎病毒，委内瑞拉脑脑炎病毒和西尼罗河病毒的比较流行病学
5. Studies on the immunogenicity in swine of influenza A virus hemagglutinin expressed by Venezuelan equine encephalitis virus-like replicon particles. [D] . Crabtree, Brenda Gail. 2007

机译：委内瑞拉马脑炎病毒样复制子颗粒表达的甲型流感病毒血凝素在猪中的免疫原性研究。
6. Possible Evidence for Interference with Venezuelan Equine Encephalitis Virus Vaccination of Equines by Pre-Existing Antibody to Eastern or Western Equine Encephalitis Virus or Both [O] . Charles H. Calisher, Donna R. Sasso, Gladys E. Sather 1973

机译：通过预先存在的东部或西部马脑炎病毒或两者的抗体干扰委内瑞拉马脑炎病毒的疫苗接种的可能证据
7. Possible Evidence for Interference with Venezuelan Equine Encephalitis Virus Vaccination of Equines by Pre-Existing Antibody to Eastern or Western Equine Encephalitis Virus, or Both [O] . Charles H. Calisher, Donna R. Sasso, Gladys E. Sather 1973

机译：通过预先存在于东部或西方标牌脑炎病毒或两者的抗体，可以干扰委内瑞拉大当量的委内瑞拉大标脑炎病毒疫苗接种
8. Novel, Rapid Assay for Detection and Differentiation of Serotype- Specific Antibodies to Venezuelan Equine Encephalitis Complex Alphaviruses [R] . Wang, E. , Paessler, S. , Smith, D. R. , 2005

机译：用于检测和鉴别委内瑞拉马脑炎复合物甲病毒血清型特异性抗体的新型快速检测方法

Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor

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