2nna
From Proteopedia
(New page: 200px<br /> <applet load="2nna" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nna, resolution 2.10Å" /> '''Structure of the MH...) |
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| - | [[Image:2nna. | + | [[Image:2nna.jpg|left|200px]]<br /><applet load="2nna" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2nna" size=" | + | |
caption="2nna, resolution 2.10Å" /> | caption="2nna, resolution 2.10Å" /> | ||
'''Structure of the MHC class II molecule HLA-DQ8 bound with a deamidated gluten peptide'''<br /> | '''Structure of the MHC class II molecule HLA-DQ8 bound with a deamidated gluten peptide'''<br /> | ||
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==Overview== | ==Overview== | ||
The risk of celiac disease is strongly associated with human leukocyte, antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the, pathogenesis of HLA-DQ2-mediated celiac disease is established, the, underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We, showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac, pathology were indeed HLA DQ8 restricted and that multiple, mostly, deamidated peptides derived from protease-sensitive sites of gliadin were, recognized. This pattern of reactivity contrasted with the more absolute, deamidation dependence and relative protease resistance of the dominant, gliadin peptide in DQ2-mediated disease. We provided a structural basis, for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The, data established that the molecular mechanisms underlying HLA-DQ8-mediated, celiac disease differed markedly from the HLA-DQ2-mediated form of the, disease. Accordingly, nondietary therapeutic interventions in celiac, disease might need to be tailored to the genotype of the individual. | The risk of celiac disease is strongly associated with human leukocyte, antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the, pathogenesis of HLA-DQ2-mediated celiac disease is established, the, underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We, showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac, pathology were indeed HLA DQ8 restricted and that multiple, mostly, deamidated peptides derived from protease-sensitive sites of gliadin were, recognized. This pattern of reactivity contrasted with the more absolute, deamidation dependence and relative protease resistance of the dominant, gliadin peptide in DQ2-mediated disease. We provided a structural basis, for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The, data established that the molecular mechanisms underlying HLA-DQ8-mediated, celiac disease differed markedly from the HLA-DQ2-mediated form of the, disease. Accordingly, nondietary therapeutic interventions in celiac, disease might need to be tailored to the genotype of the individual. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Creutzfeldt-Jakob disease, variant, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]], Multiple sclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2NNA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2NNA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NNA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: post translational modification]] | [[Category: post translational modification]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:46:10 2008'' |
Revision as of 11:46, 23 January 2008
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Structure of the MHC class II molecule HLA-DQ8 bound with a deamidated gluten peptide
Overview
The risk of celiac disease is strongly associated with human leukocyte, antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the, pathogenesis of HLA-DQ2-mediated celiac disease is established, the, underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We, showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac, pathology were indeed HLA DQ8 restricted and that multiple, mostly, deamidated peptides derived from protease-sensitive sites of gliadin were, recognized. This pattern of reactivity contrasted with the more absolute, deamidation dependence and relative protease resistance of the dominant, gliadin peptide in DQ2-mediated disease. We provided a structural basis, for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The, data established that the molecular mechanisms underlying HLA-DQ8-mediated, celiac disease differed markedly from the HLA-DQ2-mediated form of the, disease. Accordingly, nondietary therapeutic interventions in celiac, disease might need to be tailored to the genotype of the individual.
About this Structure
2NNA is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease., Henderson KN, Tye-Din JA, Reid HH, Chen Z, Borg NA, Beissbarth T, Tatham A, Mannering SI, Purcell AW, Dudek NL, van Heel DA, McCluskey J, Rossjohn J, Anderson RP, Immunity. 2007 Jul;27(1):23-34. Epub 2007 Jul 12. PMID:17629515
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