1QR1

POOR BINDING OF A HER-2/NEU EPITOPE (GP2) TO HLA-A2.1 IS DUE TO A LACK OF INTERACTIONS IN THE CENTER OF THE PEPTIDE

1QR1 の概要

• エントリーDOI: 10.2210/pdb1qr1/pdb
• 関連するPDBエントリー: 1hhg 1hhh 1hhi 1hhj 1hhk
• 分子名称: HLA-A2.1 HEAVY CHAIN, BETA-2 MICROGLOBULIN, GP2 PEPTIDE, ... (4 entities in total)
• 機能のキーワード: peptide-binding superdomain, 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; Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm: P04626
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 89235.35

構造登録者

Kuhns, J.J.,Batalia, M.A.,Yan, S.,Collins, E.J. (登録日: 1999-06-17, 公開日: 2000-01-01, 最終更新日: 2024-11-13)

主引用文献

Kuhns, J.J.,Batalia, M.A.,Yan, S.,Collins, E.J.
Poor binding of a HER-2/neu epitope (GP2) to HLA-A2.1 is due to a lack of interactions with the center of the peptide.
J.Biol.Chem., 274:36422-36427, 1999

PubMed Abstract: Class I major histocompatibility complex (MHC) molecules bind short peptides derived from proteins synthesized within the cell. These complexes of peptide and class I MHC (pMHC) are transported from the endoplasmic reticulum to the cell surface. If a clonotypic T cell receptor expressed on a circulating T cell binds to the pMHC complex, the cell presenting the pMHC is killed. In this manner, some tumor cells expressing aberrant proteins are recognized and removed by the immune system. However, not all tumors are recognized efficiently. One reason hypothesized for poor T cell recognition of tumor-associated peptides is poor binding of those peptides to class I MHC molecules. Many peptides, derived from the proto-oncogene HER-2/neu have been shown to be recognized by cytotoxic T cells derived from HLA-A2(+) patients with breast cancer and other adenocarcinomas. Seven of these peptides were found to bind with intermediate to poor affinity. In particular, GP2 (HER-2/neu residues 654-662) binds very poorly even though it is predicted to bind well based upon the presence of the correct HLA-A2.1 peptide-binding motif. Altering the anchor residues to those most favored by HLA-A2.1 did not significantly improve binding affinity. The crystallographic structure shows that unlike other class I-peptide structures, the center of the peptide does not assume one specific conformation and does not make stabilizing contacts with the peptide-binding cleft.

PubMed: 10593938
DOI: 10.1074/jbc.274.51.36422

実験手法

X-RAY DIFFRACTION (2.4 Å)