Summary
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.
Method X-RAY DIFFRACTION
Structure factors resolution 2.1 rfactor 0.2117 rfree 0.2494
DPI 0.46 theoretical min: 0.23
Citations

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