3BGM

Crystal Structure of PKD2 Phosphopeptide Bound to Human Class I MHC HLA-A2

3BGM の概要

• エントリーDOI: 10.2210/pdb3bgm/pdb
• 関連するPDBエントリー: 3BH8 3BH9 3BHA 3BHB
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, nonameric peptide from Serine/threonine-protein kinase D2, ... (5 entities in total)
• 機能のキーワード: phosphoserine, phosphopeptide, mhc, hla-a2, anchor residue, tumor antigen, glycoprotein, host-virus interaction, immune response, mhc i, polymorphism, transmembrane, ubl conjugation, immunoglobulin domain, kinase, phosphoprotein, serine/threonine-protein kinase, 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: P61769; Cytoplasm (By similarity): Q9BZL6
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44893.79

構造登録者

Mohammed, F.,Cobbold, M.,Zarling, A.L.,Salim, M.,Barrett-Wilt, G.A.,Shabanowitz, J.,Hunt, D.F.,Engelhard, V.H.,Willcox, B.E. (登録日: 2007-11-27, 公開日: 2008-10-21, 最終更新日: 2024-10-30)

主引用文献

Mohammed, F.,Cobbold, M.,Zarling, A.L.,Salim, M.,Barrett-Wilt, G.A.,Shabanowitz, J.,Hunt, D.F.,Engelhard, V.H.,Willcox, B.E.
Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self
Nat.Immunol., 9:1236-1243, 2008

PubMed Abstract: Protein phosphorylation generates a source of phosphopeptides that are presented by major histocompatibility complex class I molecules and recognized by T cells. As deregulated phosphorylation is a hallmark of malignant transformation, the differential display of phosphopeptides on cancer cells provides an immunological signature of 'transformed self'. Here we demonstrate that phosphorylation can considerably increase peptide binding affinity for HLA-A2. To understand this, we solved crystal structures of four phosphopeptide-HLA-A2 complexes. These identified a novel peptide-binding motif centered on a solvent-exposed phosphate anchor. Our findings indicate that deregulated phosphorylation can create neoantigens by promoting binding to major histocompatibility complex molecules or by affecting the antigenic identity of presented epitopes. These results highlight the potential of phosphopeptides as novel targets for cancer immunotherapy.

PubMed: 18836451
DOI: 10.1038/ni.1660

実験手法

X-RAY DIFFRACTION (1.6 Å)