PDB 3L6F deposited: 2009-12-23 modified: 2010-07-28
Title Structure of MHC class II molecule HLA-DR1 complexed with phosphopeptide MART-1
Authors Depontieu, F.R., Engelhard, V.H., Hunt, D.F., Li, Y., Mariuzza, R.A., Salay, T.M., Sette, A., Sidney, J., Topalian, S.L.
Structure factors resolution 2.1 rfactor 0.2117 rfree 0.2494
DPI 0.46 theoretical min: 0.23

Dysregulated protein phosphorylation is a hallmark of malignant transformation. Transformation can generate major histocompatibility complex (MHC)-bound phosphopeptides that are differentially displayed on tumor cells for specific recognition by T cells. To understand how phosphorylation alters the antigenic identity of self-peptides and how MHC class II molecules present phosphopeptides for CD4(+) T-cell recognition, we determined the crystal structure of a phosphopeptide derived from melanoma antigen recognized by T cells-1 (pMART-1), selectively expressed by human melanomas, in complex with HLA-DR1. The structure revealed that the phosphate moiety attached to the serine residue at position P5 of pMART-1 is available for direct interactions with T-cell receptor (TCR) and that the peptide N-terminus adopts an unusual conformation orienting it toward TCR. This structure, combined with measurements of peptide affinity for HLA-DR1 and of peptide-MHC recognition by pMART-1-specific T cells, suggests that TCR recognition is focused on the N-terminal portion of pMART-1. This recognition mode appears to be distinct from that of foreign antigen complexes but is remarkably reminiscent of the way autoreactive TCRs engage self- or altered self-peptides, consistent with the tolerogenic nature of tumor-host immune interactions.

J Mol Biol. 2010 Jun 18;399(4):596-603. Epub 2010 Apr 24.

Cross References
Database source Identifier Description
PubMed 20417641 JMOBAK
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3L6F/1 3L6F 1 trimer 0 3 0 3192