• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike
【24h】

Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike

机译：开放和封闭的结构揭示了HIV-1包膜钉的变构和柔韧性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication(1,2). The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion. Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness. Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env(3,4), and are targets of broadly neutralizing antibodies. Thus, they are attractive immunogens for vaccine development(5-8). Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 angstrom and 3.6 angstrom, respectively. We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 angstrom, 5.2 angstrom and 7.4 angstrom resolution, respectively. Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells. Both CD4 and b12 induce large, previously uncharacterized conformational rearrangements in the gp41 subunits, and the fusion peptide becomes buried in a newly formed pocket. These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
机译：对于许多包膜病毒，与宿主细胞上的受体的结合是一系列事件的第一步，这些事件最终与宿主细胞膜融合并转移遗传物质以进行复制（1,2）。 HIV表面的包膜糖蛋白（Env）三聚体负责受体结合和融合。尽管Env可以在五个可变区（V1-V5）中以及在大约占Env质量一半的N-联糖基化位点上耐受高度的突变，但是识别受体CD4和共受体CXCR4 /的功能位点CCR5是保守的，对于病毒适应性至关重要。可溶性SOSIP Env三聚体是融合前天然的，表面呈递的Env（3,4）的结构和抗原模拟物，是广泛中和抗体的目标。因此，它们是疫苗开发的诱人免疫原（5-8）。在这里，我们介绍了与CD4和抗体17b或抗体b12配合使用的B B41 SOSIP亚型三聚体B型B41 SOSIP Env三聚体的高分辨率冷冻电子显微镜结构，其分辨率分别为3.7埃和3.6埃。我们将这些与没有配体或与CD4或CD4结合位点抗体PGV04分别以5.6埃，5.2埃和7.4埃分辨率分辨的B41 SOSIP Env三聚体的冷冻电子显微镜重建相比较。因此，据我们所知，我们提供了CD4-17b诱导的中间体的最完整描述，并为HIV-1进入宿主细胞所需的受体结合诱导的构象变化提供了分子基础。 CD4和b12均可在gp41亚基中诱导大的，以前未表征的构象重排，并且融合肽被掩埋在新形成的口袋中。这些结构提供了来自HIV-1的I型病毒融合机的生物学功能的关键细节，以及用于抑制剂设计的新模板。

著录项

  • 来源
    《Nature》 |2017年第7663期|360-363|共4页
  • 作者

    Ozorowski Gabriel; Pallesen Jesper; de Val Natalia; Lyumkis Dmitry; Cottrell Christopher A.; Torres Jonathan L.; Copps Jeffrey; Stanfield Robyn L.; Cupo Albert; Pugach Pavel; Moore John P.; Wilson Ian A.; Ward Andrew B.;

  • 作者单位

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA|NanoImaging Serv, 11099 North Torrey Pines Rd,Suite 250, La Jolla, CA 92037 USA;

    Salk Inst Biol Studies, Lab Genet, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA|Salk Inst Biol Studies, Helmsley Ctr Genom Med, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA;

    Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA;

    Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA;

    Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA|Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA|Scripps Res Inst, Collaborat AIDS Vaccine Discovery, 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
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号