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Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer

机译:完全糖基化的可溶性切碎的HIV-1信封三聚体的Cryo-EM结构。

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摘要

The HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described.
机译:HIV-1包膜糖蛋白(Env)三聚体包含将病毒基因组引入宿主细胞的受体结合位点和膜融合机制。作为广泛中和抗体(bnAb)的唯一目标,Env是合理疫苗设计的重点。我们目前在5.8埃的分辨率与CD4结合位点(CD4bs)bnAb,PGV04复杂的裂解,可溶性Env三聚体(称为BG505 SOSIP.664 gp140)的冷冻电子显微镜重建和结构模型。该结构揭示了Env组分的空间排列,包括V1 / V2,V3,HR1和HR2域以及屏蔽聚糖。该结构还提供了对三聚体组装,gp120-gp41相互作用以及bnAb的CD4bs表位簇的见解,该簇覆盖了比以前描述的更大的区域并定义了更复杂的脆弱性部位。

著录项

  • 来源
    《Science》 |2013年第6165期|1484-1490|共7页
  • 作者单位

    National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA,Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA;

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA,Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA;

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA;

    Weill Medical College of Cornell University, New York, NY 10021, USA;

    National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA,Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA;

    Weill Medical College of Cornell University, New York, NY 10021, USA;

    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA,International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA,Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA,Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA;

    Weill Medical College of Cornell University, New York, NY 10021, USA,Department of Medical Microbiology, Academic Medical Center, 1105 AZ Amsterdam, Netherlands;

    Weill Medical College of Cornell University, New York, NY 10021, USA;

    National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA,Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA;

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA,Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA;

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA,International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
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  • 入库时间 2022-08-18 02:53:07

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