Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association
Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association
复制标题
DOI：
10.1074/jbc.m307457200
复制
发表时间：
2004-01-02
影响因子：
4.8
通讯作者：
Ziegler, A
中科院分区：
文献类型：
--
作者：
Hillig, RC;Hülsmeyer, M;Ziegler, A
选定的 HLA-B27 亚型与脊柱关节病相关，但其潜在机制尚不清楚。为了用分子术语解释这种关联，对不同疾病相关亚型 HLA-B*2705 和 HLA-B*2709 的肽依赖性动态和结构特性进行了比较。这些分子的区别仅在于肽结合沟底部的一个氨基酸。测定了一系列与九聚和十聚肽复合的 HLA-B27 分子的热稳定性，并揭示了取决于亚型以及肽末端残基的显着差异。此外，我们还展示了与十聚肽复合的 B*2709 亚型的晶体结构。该结构解释了 HLA-B27 偏好以 N 端精氨酸作为二级锚定点的肽，而不偏好酪氨酸作为 B*2709 中的肽 C 端。数据表明，肽复合物 HLA-B27 亚型之间的热力学特性差异与多种结构特性相关。
Selected HLA-B27 subtypes are associated with spondyloarthropathies, but the underlying mechanism is not understood. To explain this association in molecular terms, a comparison of peptide-dependent dynamic and structural properties of the differentially disease-associated subtypes HLA-B*2705 and HLA-B*2709 was carried out. These molecules differ only by a single amino acid at the floor of the peptide binding groove. The thermostabilities of a series of HLA-B27 molecules complexed with nonameric and decameric peptides were determined and revealed substantial differences depending on the subtype as well as the residues at the termini of the peptides. In addition we present the crystal structure of the B*2709 subtype complexed with a decameric peptide. This structure provides an explanation for the preference of HLA-B27 for a peptide with an N-terminal arginine as secondary anchor and the lack of preference for tyrosine as peptide C terminus in B*2709. The data show that differences in thermodynamic properties between peptide-complexed HLA-B27 subtypes are correlated with a variety of structural properties.