1h15: Difference between revisions

Revision as of 13:56, 5 November 2007

X-RAY CRYSTAL STRUCTURE OF HLA-DRA1*0101/DRB5*0101 COMPLEXED WITH A PEPTIDE FROM EPSTEIN BARR VIRUS DNA POLYMERASE

OverviewOverview

The multiple sclerosis (MS)-associated HLA major histocompatibility, complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in, strong linkage disequilibrium, making it difficult to determine which is, the principal MS risk gene. Here we show that together the DRB1 and DRB5, loci may influence susceptibility to MS. We demonstrate that a T cell, receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted, myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus, (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV, peptide complex revealed a marked degree of structural equivalence to the, DRB1*1501-MBP peptide complex at the surface presented for TCR, recognition. This provides structural evidence for molecular mimicry, involving HLA molecules. The structural details suggest an explanation for, the preponderance of MHC class II associations in HLA-associated diseases.

About this StructureAbout this Structure

1H15 is a Protein complex structure of sequences from Homo sapiens with NAG and NDG as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

A functional and structural basis for TCR cross-reactivity in multiple sclerosis., Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, Hjorth P, Sondergaard L, Svejgaard A, Wucherpfennig K, Stuart DI, Bell JI, Jones EY, Fugger L, Nat Immunol. 2002 Oct;3(10):940-3. Epub 2002 Sep 3. PMID:12244309

Page seeded by OCA on Mon Nov 5 13:01:34 2007

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OCA

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 ==Overview==
-The multiple sclerosis (MS)-associated HLA major histocompatibility, complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in, strong linkage disequilibrium, making it difficult to determine which is, the principal MS risk gene. Here we show that together the DRB1 and DRB5, loci may influence susceptibility to MS. We demonstrate that a T cell, receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted, myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus, (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV, peptide complex revealed a marked degree of structural equivalence to the, DRB1*1501-MBP peptide complex at the surface presented for TCR, recognition. This provides structural evidence for molecular mimicry, involving HLA ... [[http://ispc.weizmann.ac.il/pmbin/getpm?12244309 (full description)]]
+The multiple sclerosis (MS)-associated HLA major histocompatibility, complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in, strong linkage disequilibrium, making it difficult to determine which is, the principal MS risk gene. Here we show that together the DRB1 and DRB5, loci may influence susceptibility to MS. We demonstrate that a T cell, receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted, myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus, (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV, peptide complex revealed a marked degree of structural equivalence to the, DRB1*1501-MBP peptide complex at the surface presented for TCR, recognition. This provides structural evidence for molecular mimicry, involving HLA molecules. The structural details suggest an explanation for, the preponderance of MHC class II associations in HLA-associated diseases.
 ==About this Structure==
-H15 is a [[http://en.wikipedia.org/wiki/Protein_complex Protein complex]] structure of sequences from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with NAG and NDG as [[http://en.wikipedia.org/wiki/ligands ligands]]. Active as [[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7]]. Structure known Active Site: AC1. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H15 OCA]].
+H15 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and NDG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H15 OCA].
 ==Reference==
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 [[Category: peptide]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 15:25:16 2007''
+''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 13:01:34 2007''