2seb: Difference between revisions

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No edit summary
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|ACTIVITY=  
|ACTIVITY=  
|GENE=  
|GENE=  
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2seb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2seb OCA], [http://www.ebi.ac.uk/pdbsum/2seb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2seb RCSB]</span>
}}
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==Overview==
==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.
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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], Epiphyseal dysplasia, multiple, with myopia and deafness OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], Kniest dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], Osteoarthrosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], SED congenita OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], SED, Namaqualand type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], SMED Strudwick type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], Spondyloperipheral dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], Stickler syndrome, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]], Vitreoretinopathy with phalangeal epiphyseal dysplasia ( OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120140 120140]]


==About this Structure==
==About this Structure==
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[[Category: Wiley, D C.]]
[[Category: Wiley, D C.]]
[[Category: Zaller, D M.]]
[[Category: Zaller, D M.]]
[[Category: NAG]]
[[Category: complex (mhc class ii/superantigen)]]
[[Category: complex (mhc class ii/superantigen)]]


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