3L6F

Structure of MHC class II molecule HLA-DR1 complexed with phosphopeptide MART-1

Summary for 3L6F

• Entry DOI: 10.2210/pdb3l6f/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-1 beta chain, Melanoma antigen recognized by T-cells 1, ... (4 entities in total)
• Functional Keywords: mhc class ii, hla-dr1, phosphopeptide, disulfide bond, glycoprotein, immune response, membrane, mhc ii, transmembrane, endoplasmic reticulum, golgi apparatus, immune system-peptide binding protein complex, immune system/peptide binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903 P04229; Endoplasmic reticulum membrane; Single-pass type III membrane protein: Q16655
• Total number of polymer chains: 3
• Total formula weight: 45267.73

Authors

Li, Y.,Mariuzza, R.A. (deposition date: 2009-12-23, release date: 2010-05-12, Last modification date: 2024-11-27)

Primary citation

Li, Y.,Depontieu, F.R.,Sidney, J.,Salay, T.M.,Engelhard, V.H.,Hunt, D.F.,Sette, A.,Topalian, S.L.,Mariuzza, R.A.
Structural Basis for the Presentation of Tumor-Associated MHC Class II-Restricted Phosphopeptides to CD4(+) T Cells.
J.Mol.Biol., 399:596-603, 2010

PubMed Abstract: 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.

PubMed: 20417641
DOI: 10.1016/j.jmb.2010.04.037

Experimental method

X-RAY DIFFRACTION (2.1 Å)