STRUCTURE/BIOLOGY OF SHORT LIVED MHC II LIGAND COMPLEXES

描述（改编自研究者摘要）：拟定研究 试图扩展研究的动力学中间体结合的MHC II类分子与其抗原肽的结合。 中间复合体 具有低亲和力、快速的缔合和解离速率， 转化为稳定复合物可能涉及构象变化。 它 似乎保护II类分子在生理条件下不变性， 温度。 血凝素（HA）肽306-318的变体和血凝素肽306-318的突变体 HLA-DR 1的设计在其结合动力学和SDS方面有所不同， 稳定性和仅与HLA-DR 1和某些 肽，分别。 这些改变的肽和MHC分子将被 用于更好地理解生理意义， 短寿命肽/MHC Ⅱ类复合物的结构及其作用机制 参与肽结合。 肽的“配体交换”模型 结合将被测试，HLA-DM和部分的贡献， 将评估不变链（Ii）与肽交换。 此外该 不稳定肽/DR 1的结构将通过X射线测定 晶体学来研究不稳定结合的结构基础。 将研究短寿命复合物的生理后果。

DESCRIPTION (Adapted from Investigator's abstract): The proposed research seeks to extend studies of a kinetic intermediate in the binding of MHC class II molecules to their antigenic peptides. The intermediate complex has low affinity, fast rates of association and dissociation, and its conversion to a stable complex may involve a conformational change. It appears to preserve class II molecules from denaturation at physiological temperatures. Variants of hemagglutinin (HA) peptide 306-318 and mutants of HLA-DR1 have been designed that differ in their binding kinetics and SDS stability and that form only short-lived complexes with HLA-DR1 and certain peptides, respectively. These altered peptides and MHC molecules will be used to gain a better understanding of the physiological significance and structure of short-lived peptide/MHC class II complexes and the mechanisms involved in peptide binding. The "ligand exchange" model for peptide binding will be tested and the contribution of HLA-DM and segments of the invariant chain (Ii) to peptide exchange will be assessed. In addition, the structure of unstable peptide/DR1 will be determined by X-ray crystallography to investigate the structural basis of unstable binding. The physiological consequences of short-lived complexes will be examined.