2seb
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Genetic predisposition to rheumatoid arthritis (RA) is linked to the MHC | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Cupo, S.]] | [[Category: Cupo, S.]] | ||
[[Category: Dessen, A.]] | [[Category: Dessen, A.]] | ||
| - | [[Category: Lawrence, C | + | [[Category: Lawrence, C M.]] |
| - | [[Category: Wiley, D | + | [[Category: Wiley, D C.]] |
| - | [[Category: Zaller, D | + | [[Category: Zaller, D M.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: complex (mhc class ii/superantigen)]] | [[Category: complex (mhc class ii/superantigen)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:49:04 2008'' |
Revision as of 16:49, 21 February 2008
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X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH A PEPTIDE FROM HUMAN COLLAGEN II
Contents |
Overview
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.
Disease
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 Structure
2SEB is a Protein complex structure of sequences from Homo sapiens and Staphylococcus aureus with as ligand. Full crystallographic information is available from OCA.
Reference
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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