MHC CLASS I PEPTIDE LOADING/
MHC CLASS I PEPTIDE LOADING/
批准号:
8169311
负责人:
KARIN M REINISCH
金额:
$2.44万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-04-01 至 2011-03-31
关键词:
AccountingAffinityCatalytic DomainComplexComputer Retrieval of Information on Scientific Projects DatabaseCovalent InteractionDisulfidesERp57Family memberFundingGlycoproteinsGrantInstitutionLinkMajor Histocompatibility ComplexMolecular ModelsOxidoreductasePeptidesProcessProtein Disulfide IsomeraseResearchResearch PersonnelResolutionResourcesSourceStructureSulfhydryl CompoundsSurfaceUnited States National Institutes of Healthmolecular modelingpeptide Itapasin
中文摘要
这个子项目是许多研究子项目中利用
资源由NIH/NCRR资助的中心拨款提供。子项目和
调查员(PI)可能从NIH的另一个来源获得了主要资金,
并因此可以在其他清晰的条目中表示。列出的机构是
该中心不一定是调查人员的机构。
Tapasin是一种糖蛋白,对装载主要组织相容性复合体(MHC)I类分子具有高亲和力的多肽至关重要。它在多聚肽负载复合体(PLC)中作为二硫键连接的稳定的异二聚体与硫醇氧化还原酶ERp57结合,这种共价相互作用是支持PLC最佳活性所必需的。解决了PLC核心Tapasin-ERp57的2.6A分辨率结构。结构显示Tapasin与两个ERp57催化结构域相互作用,这是异二聚体稳定性的原因,并提供了一个蛋白质二硫键异构酶家族成员与底物相互作用的例子。突变分析发现,Tapasin上有一个与MHC-I类分子相互作用的保守表面,对于Tapasin-ERp57异源二聚体的肽装载和编辑功能至关重要。通过将Tapasin-ERp57结构与其他已定义的PLC组分的结构相结合,我们提出了一个分子模型,该模型解释了MHC I类多肽负载的过程。
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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会议论文
Molecular Basis for Membrane Lipid Homeostasis
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批准号:10373995
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项目类别:
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资助金额:$81.92万
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财政年份:2019
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负责人:KARIN M REINISCH
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依托单位:
Molecular Basis for Membrane Lipid Homeostasis
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批准号:10580720
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项目类别:
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资助金额:$81.92万
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财政年份:2019
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负责人:KARIN M REINISCH
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依托单位:
Molecular Basis for Membrane Lipid Homeostasis
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批准号:9898415
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项目类别:
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资助金额:$81.92万
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财政年份:2019
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负责人:KARIN M REINISCH
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依托单位:
Pathophysiology of Plasma Membrane PI4P Generation
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批准号:9278254
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项目类别:
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资助金额:$50.81万
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财政年份:2015
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负责人:KARIN M REINISCH
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依托单位:
Pathophysiology of Plasma Membrane PI4P Generation
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批准号:9069989
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项目类别:
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资助金额:$50.81万
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财政年份:2015
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负责人:KARIN M REINISCH
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依托单位:
THIOREDUCTASE EXPRESSED IN SF21 CELLS
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批准号:8363345
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项目类别:
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资助金额:$0.21万
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财政年份:2011
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负责人:KARIN M REINISCH
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依托单位:
SNARE PRE-FUSION INTERMEDIATE WITH INHIBITORY PEPTIDES
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批准号:8170615
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项目类别:
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资助金额:$0.41万
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财政年份:2010
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负责人:KARIN M REINISCH
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依托单位:
Structural studies of the MHC class I peptide loading complex
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批准号:7873965
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项目类别:
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资助金额:$20.69万
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财政年份:2010
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负责人:KARIN M REINISCH
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依托单位:
Structural studies of the MHC class I peptide loading complex
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批准号:8066717
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项目类别:
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资助金额:$24.58万
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财政年份:2010
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负责人:KARIN M REINISCH
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依托单位:
STRUCTURAL STUDIES OF THE TRAPP MEMBRANE TETHERING COMPLEX
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批准号:7955207
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项目类别:
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资助金额:$0.49万
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财政年份:2009
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负责人:KARIN M REINISCH
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依托单位:
Assembly and Architecture of the Exocyst, a Membrane Tethering Complex
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批准号:7923641
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项目类别:
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资助金额:$28.84万
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财政年份:2009
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负责人:KARIN M REINISCH
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依托单位:
STRUCTURAL STUDIES OF THE EXOCYST COMPLEX
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批准号:7955084
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项目类别:
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资助金额:$0.49万
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财政年份:2009
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负责人:KARIN M REINISCH
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依托单位:
STRUCTURAL STUDIES OF THE EXOCYST COMPLEX
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批准号:7721204
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项目类别:
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资助金额:$1.41万
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财政年份:2008
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负责人:KARIN M REINISCH
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依托单位:
STRUCTURAL STUDIES FOR THE EXOCYST COMPLEX
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批准号:7726252
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项目类别:
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资助金额:$0.4万
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财政年份:2008
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负责人:KARIN M REINISCH
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依托单位:
Assembly and Architecture of the Exocyst, a Membrane Tethering Complex
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批准号:7904253
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项目类别:
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资助金额:$31.13万
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财政年份:2007
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负责人:KARIN M REINISCH
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依托单位:
Assembly and Architecture of the Exocyst, a Membrane Tethering Complex
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批准号:7468399
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项目类别:
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资助金额:$31.45万
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财政年份:2007
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负责人:KARIN M REINISCH
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依托单位:
STRUCTURAL STUDIES FOR THE EXOCYST COMPLEX
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批准号:7602319
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项目类别:
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资助金额:$0.31万
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财政年份:2007
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负责人:KARIN M REINISCH
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依托单位:
Assembly and Architecture of the Exocyst, a Membrane Tethering Complex
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批准号:7663729
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项目类别:
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资助金额:$31.45万
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财政年份:2007
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负责人:KARIN M REINISCH
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依托单位:
Lipid transporters and lipid homeostasis at membrane contact sites
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批准号:9102300
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项目类别:
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资助金额:$37.77万
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财政年份:2007
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负责人:KARIN M REINISCH
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依托单位:
Regulatory Mechanisms in Membrane Trafficking
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批准号:8450764
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项目类别:
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资助金额:$33.9万
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财政年份:2007
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负责人:KARIN M REINISCH
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依托单位:
海外基金