NMR spectroscopic investigation of micropolymorphism-dependent dynamics of human major histocompatibility antigens

人类主要组织相容性抗原微多态性依赖性动力学的核磁共振波谱研究

• 批准号: 158991469
• 负责人: Dr. Peter Schmieder
• 金额: --
• 依托单位: Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/158991469?language=en
• 关键词: NMR; spectroscopic; investigation; micropolymorphism; dependent

Antigens encoded by the major histocompatibility complex (MHC, HLA complex in human) play a central role in the immune response. MHC class I molecules accommodate small peptide fragments of 8 to 12 amino acids within a binding groove and present them to T cell receptors on cytotoxic T cells. T cells constitute a necessary component of normal adaptive immune responses, but can also be involved in autoimmunity. A wealth of structural information on MHC:peptide complexes has become available, but the static picture resulting from crystallographic studies has not been able to fully explain several features of the interaction between these molecules. We will employ heteronuclear NMR spectroscopy in conjunction with extensive labeling to investigate the dynamics of the peptide and the MHC class I binding groove at physiological temperature. By comparing peptides in complex with HLA-B27 subtypes that differ only by a single amino acid exchange from each other, but are differentially associated with an autoimmune disease, we will correlate the dynamic and structural attributes with distinct functional properties of these peptide-loaded molecules.

由主要组织相容性复合体（MHC，人类的HLA复合体）编码的抗原在免疫应答中起核心作用。MHC I类分子在结合沟内容纳8至12个氨基酸的小肽片段，并将其呈递给细胞毒性T细胞上的T细胞受体。T细胞构成正常适应性免疫应答的必要组成部分，但也可参与自身免疫。丰富的MHC：肽复合物的结构信息已经成为可用的，但从晶体学研究产生的静态图片还没有能够充分解释这些分子之间的相互作用的几个功能。我们将采用异相NMR光谱结合广泛的标记，以研究在生理温度下的肽和MHC I类结合沟的动力学。通过比较与HLA-B27亚型复合的肽，这些肽仅通过单个氨基酸交换彼此不同，但与自身免疫性疾病差异相关，我们将这些肽负载分子的动态和结构属性与不同的功能特性相关联。

项目成果

Structural and dynamic features of HLA-B27 subtypes

HLA-B27亚型的结构和动态特征

• DOI: 10.1097/bor.0b013e32836203ab
• 发表时间: 2013
• 期刊: Current Opinion in Rheumatology
• 影响因子: 5.1
• 作者: Uchanska-Ziegler;Ziegler;Schmieder
• 通讯作者: Schmieder

Dynamics of free versus complexed β2-microglobulin and the evolution of interfaces in MHC class I molecules

• DOI: 10.1007/s00251-012-0667-4
• 发表时间: 2013-03-01
• 期刊: IMMUNOGENETICS
• 影响因子: 3.2
• 作者: Hee, Chee-Seng;Beerbaum, Monika;Ziegler, Andreas
• 通讯作者: Ziegler, Andreas

HLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system.

疑似自身免疫病因的 HLA I 类相关疾病：HLA-B27 亚型作为模型系统

• DOI: 10.1016/j.ejcb.2011.03.003
• 发表时间: 2012
• 期刊: European journal of cell biology
• 影响因子: 6.6
• 作者: Uchanska-Ziegler;Fabian;Saenger;Ziegler
• 通讯作者: Ziegler

IR spectroscopic analyses of amyloid fibril formation of β2-microglobulin using a simplified procedure for its in vitro generation at neutral pH.

使用简化程序在中性 pH 下进行体外生成，对 β2 微球蛋白的淀粉样原纤维形成进行红外光谱分析

• DOI: 10.1016/j.bpc.2013.05.001
• 发表时间: 2013
• 期刊: Biophysical chemistry
• 影响因子: 3.8
• 作者: Fabian;Jetzschmann;Naumann;Ziegler;Uchanska-Ziegler
• 通讯作者: Uchanska-Ziegler