2seb
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X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH A PEPTIDE FROM HUMAN COLLAGEN II
OverviewOverview
Genetic predisposition to rheumatoid arthritis (RA) is linked to the MHC, class II allele HLA-DR4. The charge of the amino acid at DRbeta71 in the, peptide-binding site appears to be critical in discriminating DR molecules, linked to increased disease susceptibility. We have determined the 2.5 A, x-ray structure of the DR4 molecule with the strongest linkage to RA, (DRB1*0401) complexed with a human collagen II peptide. Details of a, predicted salt bridge between lysine DRbeta71 and aspartic acid at the P4, peptide position suggest how it may participate in both antigen binding, and TCR activation. A model is proposed for the DR4 recognition of, collagen II (261-273), an antigen immunodominant in human-transgenic mouse, models of RA.
DiseaseDisease
Known diseases associated with this structure: Achondrogenesis-hypochondrogenesis, type II OMIM:[120140], Epiphyseal dysplasia, multiple, with myopia and deafness OMIM:[120140], Kniest dysplasia OMIM:[120140], Osteoarthrosis OMIM:[120140], Platys OMIM:[120140], SED congenita OMIM:[120140], SMD OMIM:[120140], SMED Strudwick type OMIM:[120140], Spondyloperipheral dysplasia OMIM:[120140], Stickler syndrome, type I OMIM:[120140], Vitreoretinopathy with phalangeal epiphyseal dysplasia OMIM:[120140]
About this StructureAbout this Structure
2SEB is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus with NAG as ligand. Full crystallographic information is available from OCA.
ReferenceReference
X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II., Dessen A, Lawrence CM, Cupo S, Zaller DM, Wiley DC, Immunity. 1997 Oct;7(4):473-81. PMID:9354468
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