1qr1
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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
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Adenocarcinoma of lung, somatic OMIM:[164870], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Gastric cancer, somatic OMIM:[164870], Glioblastoma, somatic OMIM:[164870], Hypoproteinemia, hypercatabolic OMIM:[109700], Ovarian cancer, somatic, OMIM:[164870], Sialidosis, type I OMIM:[608272], Sialidosis, type II OMIM:[608272], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this StructureAbout this Structure
1QR1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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., Kuhns JJ, Batalia MA, Yan S, Collins EJ, J Biol Chem. 1999 Dec 17;274(51):36422-7. PMID:10593938
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