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

Summary for 1QR1

• Entry DOI: 10.2210/pdb1qr1/pdb
• Related: 1hhg 1hhh 1hhi 1hhj 1hhk
• Descriptor: HLA-A2.1 HEAVY CHAIN, BETA-2 MICROGLOBULIN, GP2 PEPTIDE, ... (4 entities in total)
• Functional Keywords: peptide-binding superdomain, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: 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
• Total number of polymer chains: 6
• Total formula weight: 89235.35

Authors

Kuhns, J.J.,Batalia, M.A.,Yan, S.,Collins, E.J. (deposition date: 1999-06-17, release date: 2000-01-01, Last modification date: 2021-11-03)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)