Structure-function studies of the membrane-interacting domains of HIV-1 Env spike

HIV-1 Env 刺突膜相互作用域的结构功能研究

基本信息

  • 批准号:
    10326632
  • 负责人:
  • 金额:
    $ 83.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-05-20 至 2026-06-30
  • 项目状态:
    未结题

项目摘要

Project Summary The first critical step for enveloped viruses, such as HIV-1, to enter host cells is viral membrane fusion. Viral fusion proteins are fascinating protein folding machineries capable of adopting completely different conformations during the fusion process; they are also important vaccine and therapeutic targets. Previous studies have revealed both pre- and post-fusion conformations of the soluble fragments of many viral fusion proteins, but less is known for structures of their fusion peptide, transmembrane and membrane-proximal regions in the context of lipid bilayers. There is strong evidence for functional roles of the membrane- interacting regions in fusion, and yet mechanistic studies on how they exert their functions remain scarce. We hypothesize that membrane-interacting regions of other fusion proteins related to HIV-1 envelope protein (Env) adopt defined oligomeric structures that are critical for the stability, function and antigenicity of the full-length proteins in membrane. In the studies that we completed during the previous funding period, we have determined the structures of the TM, membrane proximal external region, and cytoplasmic tail of HIV-1 Env in bicelles that mimic lipid bilayers using the latest NMR technology. We find that these regions all form well-ordered trimeric clusters and are conformationally coupled, and that disrupting them can reduce fusion and alter the antigenic structure of the entire Env. In this application, we propose to apply our NMR/bicelle technology to investigate the membrane regions of SIV Env and the recently emerged SARS- CoV-2 spike (S), and to use cryo-electron microscopy to determine structures of the full-length proteins reconstituted in lipid nanodiscs. We will define roles in membrane fusion of critical structural elements of these regions by deep mutagenesis and functional assays. We will purse the following specific aims: 1) we will investigate the membrane-interacting components of SIV Env; 2) we will investigate the membrane-interacting components in the postfusion arrangement; 3) we will determine structures of the full-length SIV Env and SARS-CoV-2 S in the context of membrane; 4) we will elucidate roles of the membrane-interacting domains of HIV/SIV Env and SARS-CoV-2 S in their stability, function and antigenicity.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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JAMES Jeiwen CHOU其他文献

JAMES Jeiwen CHOU的其他文献

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{{ truncateString('JAMES Jeiwen CHOU', 18)}}的其他基金

Structural and Functional Roles of the Membrane-Related Components of Single-Pass Membrane Proteins
单程膜蛋白膜相关成分的结构和功能作用
  • 批准号:
    10380877
  • 财政年份:
    2021
  • 资助金额:
    $ 83.42万
  • 项目类别:
CONTROL AND ACTIVATION OF THE TUMOR NECROSIS FACTOR RECEPTORS
肿瘤坏死因子受体的控制和激活
  • 批准号:
    10338106
  • 财政年份:
    2020
  • 资助金额:
    $ 83.42万
  • 项目类别:
CONTROL AND ACTIVATION OF THE TUMOR NECROSIS FACTOR RECEPTORS
肿瘤坏死因子受体的控制和激活
  • 批准号:
    10092951
  • 财政年份:
    2020
  • 资助金额:
    $ 83.42万
  • 项目类别:
Structure-function studies of the membrane-interacting domains of HIV-1 Env spike
HIV-1 Env 刺突膜相互作用域的结构功能研究
  • 批准号:
    9203214
  • 财政年份:
    2016
  • 资助金额:
    $ 83.42万
  • 项目类别:
Structure-function studies of the membrane-interacting domains of HIV-1 Env spike
HIV-1 Env 刺突膜相互作用域的结构功能研究
  • 批准号:
    9899171
  • 财政年份:
    2016
  • 资助金额:
    $ 83.42万
  • 项目类别:
Structure-function studies of the membrane-interacting domains of HIV-1 Env spike
HIV-1 Env 刺突膜相互作用域的结构功能研究
  • 批准号:
    9275921
  • 财政年份:
    2016
  • 资助金额:
    $ 83.42万
  • 项目类别:
Function and mechanism of the HCV p7 channel and its therapeutic potential
HCV p7通道的功能、机制及其治疗潜力
  • 批准号:
    9198039
  • 财政年份:
    2016
  • 资助金额:
    $ 83.42万
  • 项目类别:
Function and mechanism of the HCV p7 channel and its therapeutic potential
HCV p7通道的功能、机制及其治疗潜力
  • 批准号:
    8880443
  • 财政年份:
    2014
  • 资助金额:
    $ 83.42万
  • 项目类别:
Project 2
项目2
  • 批准号:
    8151958
  • 财政年份:
    2010
  • 资助金额:
    $ 83.42万
  • 项目类别:
Membrane protein structures by solution NMR
通过溶液 NMR 确定膜蛋白结构
  • 批准号:
    8140470
  • 财政年份:
    2010
  • 资助金额:
    $ 83.42万
  • 项目类别:

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