3MYJ

Human Class I MHC HLA-A2 in complex with the WT-1 (126-134) (R1Y) peptide variant.

3MYJ の概要

• エントリーDOI: 10.2210/pdb3myj/pdb
• 関連するPDBエントリー: 1TVB 3HPJ
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Wilms tumor protein, ... (5 entities in total)
• 機能のキーワード: wt-1 peptide, r1y mutation, nonapeptide, mhc class i, hla-a2, cancer vaccine, disulfide bond, glycoprotein, host-virus interaction, immune response, membrane, mhc i, phosphoprotein, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, immune system
• 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: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769; Nucleus . Isoform 1: Nucleus speckle . Isoform 4: Nucleus, nucleoplasm : P19544
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 89789.81

構造登録者

Borbulevych, O.Y.,Baker, B.M. (登録日: 2010-05-10, 公開日: 2010-08-18, 最終更新日: 2024-11-06)

主引用文献

Borbulevych, O.Y.,Do, P.,Baker, B.M.
Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: Implications for WT1-based cancer therapeutics.
Mol.Immunol., 47:2519-2524, 2010

PubMed Abstract: Presentation of peptides by class I or class II major histocompatibility complex (MHC) molecules is required for the initiation and propagation of a T cell-mediated immune response. Peptides from the Wilms Tumor 1 transcription factor (WT1), upregulated in many hematopoetic and solid tumors, can be recognized by T cells and numerous efforts are underway to engineer WT1-based cancer vaccines. Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding. The R1Y variant, a potential vaccine candidate, alters the positions of MHC charged side chains near the peptide N-terminus and significantly reduces the peptide/MHC electrostatic surface potential. These alterations indicate that the R1Y variant is an imperfect mimic of the native WT1 peptide, and suggest caution in its use as a therapeutic vaccine. Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.

PubMed: 20619457
DOI: 10.1016/j.molimm.2010.06.005

実験手法

X-RAY DIFFRACTION (1.89 Å)