MECHANISM OF PEPTIDE LOADING ONTO HUMAN MHC CLASS II MOLECULES

肽加载到人类 MHC II 类分子上的机制

• 批准号: 8361725
• 负责人: Kai W Wucherpfennig
• 金额: $ 0.55万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361725
• 关键词: Binding; CLIP peptide; Excision; Funding; Goals; Grant; Histocompatibility Antigens Class II; Human; Left; Molecular; N-terminal; National Center for Research Resources; Peptide Hydrolases; Peptides; Principal Investigator; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; base; cost; insight; invariant chain; microbial; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the project is to determine the mechanisms of peptide loading onto human MHC class II molecules. MHC class II molecules bind peptides very tightly, with half-lives of several days to weeks. Empty MHC class II molecules have a tendency to aggregate and they assemble in the ER with invariant chain, which occupies the binding groove like a peptide. In the endosomal peptide loading compartment, invariant chain is degraded by a set of proteases, leaving the CLIP peptide of invariant chain in the groove. Removal of the CLIP peptide requires the action of HLA-DM and makes the binding groove vacant for binding of microbial peptides. We have defined the molecular requirements for the interaction of MHC class II molecules with HLA-DM. We found that HLA-DM binding required release of the N-terminal part of the peptide. Based on this insight, we are now attempting to characterize this interaction at a structural level.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目的目标是确定肽加载到人类MHC II类分子上的机制。 MHC II类分子与肽结合非常紧密，半衰期为数天至数周。 空的MHC II类分子具有聚集的趋势，并且它们在ER中组装有不变链，其像肽一样占据结合沟。 在内体肽装载区室中，不变链被一组蛋白酶降解，将不变链的CLIP肽留在凹槽中。 CLIP肽的去除需要HLA-DM的作用，并使结合沟空置以结合微生物肽。 我们已经确定了MHC II类分子与HLA-DM相互作用的分子要求。 我们发现HLA-DM结合需要释放肽的N末端部分。 基于这一认识，我们现在正试图在结构层面上描述这种相互作用。