1W0W

Crystal Structure Of HLA-B*2709 Complexed With the self-Peptide TIS from EGF-response factor 1

1W0W の概要

• エントリーDOI: 10.2210/pdb1w0w/pdb
• 関連するPDBエントリー: 1HSA 1JGD 1JGE 1K5N 1OF2 1OGT 1RGO 1ROG 1ROH 1ROI 1ROJ 1ROK 1ROL 1UXS 1UXW 1W0V
• 分子名称: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, BETA-2-MICROGLOBULIN, BUTYRATE RESPONSE FACTOR 2, ... (5 entities in total)
• 機能のキーワード: immune system, mhc, major histocompatibility complex, hla- b*2705, mhc i
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P03989; Secreted: P61769; Nucleus (Potential): P47974
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45175.20

構造登録者

Hulsmeyer, M.,Fiorillo, M.T.,Bettosini, F.,Sorrentino, R.,Saenger, W.,Ziegler, A.,Uchanska-Ziegler, B. (登録日: 2004-06-14, 公開日: 2005-03-07, 最終更新日: 2024-10-09)

主引用文献

Hulsmeyer, M.,Welfle, K.,Pohlmann, T.,Misselwitz, R.,Alexiev, U.,Welfle, H.,Saenger, W.,Uchanska-Ziegler, B.,Ziegler, A.
Thermodynamic and Structural Equivalence of Two Hla-B27 Subtypes Complexed with a Self-Peptide
J.Mol.Biol., 346:1367-, 2005

PubMed Abstract: The F pocket of major histocompatibility complex (in humans HLA) class I molecules accommodates the C terminus of the bound peptide. Residues forming this pocket exhibit considerable polymorphism, and a single difference (Asp116 in HLA-B*2705 and His116 in HLA-B*2709 heavy chains) confers differential association of these two HLA-B27 subtypes to the autoimmune disease ankylosing spondylitis. As peptide presentation by HLA molecules is of central importance for immune responses, we performed thermodynamic (circular dichroism, differential scanning calorimetry, fluorescence polarization) and X-ray crystallographic analyses of both HLA-B27 subtypes complexed with the epidermal growth factor response factor 1-derived self-peptide TIS (RRLPIFSRL) to understand the impact of the Asp116His exchange on peptide display. This peptide is known to be presented in vivo by both subtypes, and as expected for a self-peptide, TIS-reactive cytotoxic T lymphocytes are absent in the respective individuals. The thermodynamic analyses reveal that both HLA-B27:TIS complexes exhibit comparable, relatively high thermostability (Tm approximately 60 degrees C) and undergo multi-step unfolding reactions, with dissociation of the peptide in the first step. As shown by X-ray crystallography, only subtle structural differences between the subtypes were observed regarding the architecture of their F pockets, including the presence of distinct networks of water molecules. However, no consistent structural differences were found between the peptide presentation modes. In contrast to other peptides displayed by the two HLA-subtypes which show either structural or dynamical differences in their peptide presentation modes, the TIS-complexed HLA-B*2705 and HLA-B*2709 subtypes are an example for thermodynamic and structural equivalence, in agreement with functional data.

PubMed: 15713487
DOI: 10.1016/J.JMB.2004.12.047

実験手法

X-RAY DIFFRACTION (2.11 Å)