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Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer

机译:可溶性切割的HIV-1信封三聚体的晶体结构。

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摘要

HIV-1 entry into CD4~+ target cells is mediated by cleaved envelope gtycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP.664 gpl40 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gpl20 and gp41 subunits, and how a close association between the gpl20 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gpl20 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design.
机译:HIV-1进入CD4〜+靶细胞的过程是由被切开的包膜糖蛋白(Env)三聚体介导的,该三聚体在结构上难以表征。在这里,我们描述了与有效的广泛中和抗体PGT122形成复合体的,稳定且抗原性接近天然的可溶,裂解的Env三聚体(称为BG505 SOSIP.664 gpl40三聚体)在4.7埃处的晶体结构。该结构显示gp41的预融合状态,gp120和gp41亚基之间的相互作用,以及gp120 V1 / V2 / V3环之间的紧密结合如何稳定三聚体围绕三重轴的顶点。三聚体上PGT122的完整表位涉及gp120 V1,V3和一些周围的聚糖。这种三聚体结构提高了我们对Env的功能和免疫系统的理解,并为基于结构的疫苗设计提供了蓝图。

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  • 来源
    《Science》 |2013年第6165期|1477-1483|共7页
  • 作者单位

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,International AIDS Vaccine Initiative Neutralizing Antibody Center, 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;

    International AIDS Vaccine Initiative Neutralizing Antibody Center, 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,Department of Immunology and Microbial Science, 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,International AIDS Vaccine Initiative Neutralizing Antibody Center, 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;

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

    Joint Center for Structural Genomics, The Scripps Research Institute, La Jolla, CA 92037, USA;

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

    International AIDS Vaccine Initiative Neutralizing Antibody Center, 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,Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA,Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02129, USA;

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

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

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,International AIDS Vaccine Initiative Neutralizing Antibody Center, 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;

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA,International AIDS Vaccine Initiative Neutralizing Antibody Center, 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,Joint Center for Structural Genomics, The Scripps Research Institute, La Jolla, CA 92037, USA,Skaggs Institute for Chemical Biology, 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);
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  • 正文语种 eng
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  • 入库时间 2022-08-18 02:53:07

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