1aqd
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HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142800], Ankylosing spondylitis, susceptibility to, 1 OMIM:[142800], Stevens-Johnson syndrome, susceptibility to OMIM:[142800]
About this StructureAbout this Structure
1AQD is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding., Murthy VL, Stern LJ, Structure. 1997 Oct 15;5(10):1385-96. PMID:9351812
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