Summary
PDB 1AQD deposited: 1997-07-28 modified: 2009-02-24
Title HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE
Authors Murthy, V.L., Stern, L.J.
Method X-RAY DIFFRACTION
Structure factors resolution 2.45 rfactor 0.216 rfree 0.279
DPI 0.86 theoretical min: 0.37
Citations

BACKGROUND: Class II major histocompatibility complex (MHC) proteins are cell surface glycoproteins that bind peptides and present them to T cells as part of the mechanism for detecting and responding to foreign material in the body. The peptide-binding activity exhibits allele-specific preferences for particular sidechains at some positions, although the structural basis of these preferences is not understood in detail. We have determined the 2.45 A crystal structure of the human class II MHC protein HLA-DR1 in complex with the tight binding endogenous peptide A2 (103-117) in order to discover peptide-MHC interactions that are important in determining the binding motif and to investigate conformational constraints on the bound peptide. RESULTS: The bound peptide adopts a polyproline II-like conformation and places several sidechains within pockets in the binding site. Bound water molecules mediate MHC-peptide contacts at several sites. A tryptophan residue from the beta 2 'lower' domain of HLA-DR1 was found to project into a pocket underneath the peptide-binding domain and may be important in modulating interdomain interactions in MHC proteins. CONCLUSIONS: The peptide-binding motif of HLA-DR1 includes an aromatic residue at position +1, an arginine residue at position +2, and a small residue at position +6 (where the numbering refers to the normal MHC class II convention); these preferences can be understood in light of interactions observed in the peptide-MHC complex. Comparison of the structure with that of another MHC-peptide complex shows that completely different peptide sequences bind in essentially the same conformation and are accommodated with only minimal rearrangement of HLA-DR1 residues. Small conformational differences that are observed appear to be important in interactions with other proteins.

Structure. 1997 Oct 15;5(10):1385-96.

Cross References
Database source Identifier Description
PubMed 9351812 STRUE6
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1AQD/1 1AQD 1 trimer 0 3 0 3016
1AQD/2 1AQD 2 trimer 0 3 0 3022
1AQD/3 1AQD 3 trimer 0 3 0 3014
1AQD/4 1AQD 4 trimer 0 3 0 3002