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中文摘要
翻译
该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者(PI)可能从另一个NIH来源获得主要资金, 因此可以在其他CRISP条目中表示。列出的机构是 中心,不一定是研究者的机构。 Tapasin是一种糖蛋白,对于装载具有高亲和力肽的主要组织相容性复合体(MHC)I类分子至关重要。它在多聚体肽负载复合物(PLC)中作为二硫键连接的稳定异源二聚体与硫醇氧化还原酶ERp 57一起发挥作用,并且需要这种共价相互作用来支持最佳PLC活性。我们已经解决了PLC的Tapasin-ERp 57核心的2.6 A分辨率结构。该结构揭示了tapasin与两个ERp 57催化结构域相互作用,解释了异二聚体的稳定性,并提供了蛋白质二硫键异构酶家族成员与底物相互作用的实例。突变分析鉴定了tapasin上与MHC I类分子相互作用的保守表面,并且对于tapasin-ERp 57异二聚体的肽加载和编辑功能至关重要。通过将Tapasin-ERp 57结构与其他定义的PLC组件相结合,我们提出了一个分子模型,阐明了MHC I类肽加载过程。
英文摘要
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tapasin is a glycoprotein critical for loading major histocompatibility complex (MHC) class I molecules with high-affinity peptides. It functions within the multimeric peptide-loading complex (PLC) as a disulfide-linked, stable heterodimer with the thiol oxidoreductase ERp57, and this covalent interaction is required to support optimal PLC activity. We have solved the 2.6 A resolution structure of the tapasin-ERp57 core of the PLC. The structure revealed that tapasin interacts with both ERp57 catalytic domains, accounting for the stability of the heterodimer, and provided an example of a protein disulfide isomerase family member interacting with substrate. Mutational analysis identified a conserved surface on tapasin that interacted with MHC class I molecules and was critical for peptide loading and editing functions of the tapasin-ERp57 heterodimer. By combining the tapasin-ERp57 structure with those of other defined PLC components, we present a molecular model that illuminates the processes involved in MHC class I peptide loading.
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Molecular Basis for Membrane Lipid Homeostasis
  • 批准号:
    10373995
  • 项目类别:
  • 资助金额:
    $81.92万
  • 财政年份:
    2019
  • 负责人:
    KARIN M REINISCH
  • 依托单位:
Molecular Basis for Membrane Lipid Homeostasis
  • 批准号:
    10580720
  • 项目类别:
  • 资助金额:
    $81.92万
  • 财政年份:
    2019
  • 负责人:
    KARIN M REINISCH
  • 依托单位:
Molecular Basis for Membrane Lipid Homeostasis
  • 批准号:
    9898415
  • 项目类别:
  • 资助金额:
    $81.92万
  • 财政年份:
    2019
  • 负责人:
    KARIN M REINISCH
  • 依托单位:
Pathophysiology of Plasma Membrane PI4P Generation
  • 批准号:
    9278254
  • 项目类别:
  • 资助金额:
    $50.81万
  • 财政年份:
    2015
  • 负责人:
    KARIN M REINISCH
  • 依托单位:
海外基金