3FQX

Phosphorylation of self-peptides alters Human Leukocyte Antigen Class I-restricted antigen presentation and generates tumor specific epitopes

3FQX の概要

• エントリーDOI: 10.2210/pdb3fqx/pdb
• 関連するPDBエントリー: 3FQN 3FQR 3FQT 3FQU 3FQW
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, phospho-peptide 1097-1105 from insulin receptor substrate 2 (IRS2): RVA(Sep)PTSGV, ... (7 entities in total)
• 機能のキーワード: immune system, phosphorylation, glycoprotein, immune response, membrane, mhc i, phosphoprotein, transmembrane, disease mutation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, cancer, tcr, self-epitope
• 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
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45238.01

構造登録者

Petersen, J.,Rossjohn, J. (登録日: 2009-01-07, 公開日: 2009-03-03, 最終更新日: 2024-10-16)

主引用文献

Petersen, J.,Wurzbacher, S.J.,Williamson, N.A.,Ramarathinam, S.H.,Reid, H.H.,Nair, A.K.,Zhao, A.Y.,Nastovska, R.,Rudge, G.,Rossjohn, J.,Purcell, A.W.
Phosphorylated self-peptides alter human leukocyte antigen class I-restricted antigen presentation and generate tumor-specific epitopes
Proc.Natl.Acad.Sci.Usa, 106:2776-2781, 2009

PubMed Abstract: Human leukocyte antigen (HLA) class I molecules present a variety of posttranslationally modified epitopes at the cell surface, although the consequences of such presentation remain largely unclear. Phosphorylation plays a critical cellular role, and deregulation in phosphate metabolism is associated with disease, including autoimmunity and tumor immunity. We have solved the high-resolution structures of 3 HLA A2-restricted phosphopeptides associated with tumor immunity and compared them with the structures of their nonphosphorylated counterparts. Phosphorylation of the epitope was observed to affect the structure and mobility of the bound epitope. In addition, the phosphoamino acid stabilized the HLA peptide complex in an epitope-specific manner and was observed to exhibit discrete flexibility within the antigen-binding cleft. Collectively, our data suggest that phosphorylation generates neoepitopes that represent demanding targets for T-cell receptor ligation. These findings provide insights into the mode of phosphopeptide presentation by HLA as well as providing a platform for the rational design of a generation of posttranslationally modified tumor vaccines.

PubMed: 19196958
DOI: 10.1073/pnas.0812901106

実験手法

X-RAY DIFFRACTION (1.7 Å)