BINDING INTERACTIONS WITHIN PEPTIDE-MHC COMPLEXES

肽-MHC 复合物内的结合相互作用

• 批准号: 6127991
• 负责人: Craig Cano Beeson
• 金额: $ 22.42万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6127991
• 关键词: MHC class II antigen; antigen presentation; electron spin resonance spectroscopy; hydrogen bond; peptides; protein binding; thermodynamics

The objective of this research is to define the relative energetics of binding interactions between peptides and MHC class II proteins. Helper T cells are activated by the interaction of an antigen receptor on the T cell with ligands expressed on the surface of other cells. These ligands are complexes of peptides bound to MHC class II proteins. The peptide is bound in a groove on the membrane distal face of the protein. Binding interactions include an array of hydrogen bonds from MHC sidechains to the peptide backbone and pockets in the peptide-binding groove on which peptide sidechains reside. While much is known about the structure of these complexes, the relative contributions of the different binding interactions to the overall stabilities of the complexes are not unknown. We propose to systematically eliminate specific hydrogen-bond and pocket interactions for a variety of peptide-MHC complexes and evaluate their contribution the stabilities. These results will define the rules for peptide binding to MHC class II proteins. The binding rules will greatly aid analyses of antigenic peptide-MHC complexes and the identification of T-cell epitopes.

本研究的目的是确定多肽与MHC-II类蛋白结合相互作用的相对能量学。辅助性T细胞通过T细胞上的抗原受体与其他细胞表面表达的配体相互作用而被激活。这些配体是与MHC II类蛋白结合的多肽的复合体。该多肽结合在蛋白质膜远端的凹槽中。结合作用包括从MHC侧链到多肽骨架的一系列氢键，以及位于多肽侧链的多肽结合槽中的口袋。虽然对这些络合物的结构有很多了解，但不同的结合作用对络合物整体稳定性的相对贡献并不是未知的。我们建议系统地消除各种多肽-MHC络合物的特定氢键和口袋相互作用，并评估它们对稳定性的贡献。这些结果将定义多肽与MHC II类蛋白结合的规则。结合规则将大大有助于抗原肽-MHC复合体的分析和T细胞表位的识别。