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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 05011naa a2200637 4500 | |
| 001 | oai:gup.ub.gu.se/142715 | |
| 003 | SwePub | |
| 008 | 240410s2011 | |||||||||||000 ||eng| | |
| 009 | oai:research.chalmers.se:7b066eb2-f5d8-4edb-8080-535ae55ffda7 | |
| 009 | oai:prod.swepub.kib.ki.se:122688149 | |
| 024 | 7 | a https://gup.ub.gu.se/publication/1427152 URI |
| 024 | 7 | a https://doi.org/10.1002/hep.242992 DOI |
| 024 | 7 | a https://research.chalmers.se/publication/1427152 URI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1226881492 URI |
| 040 | a (SwePub)gud (SwePub)cthd (SwePub)ki | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Hov, J. R.u Oslo universitetssykehus,Oslo University Hospital,Universitetet i Oslo,University of Oslo4 aut |
| 245 | 1 0 | a Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis |
| 264 | c 2011-05-13 | |
| 264 | 1 | b Ovid Technologies (Wolters Kluwer Health),c 2011 |
| 520 | a The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 x 10(-32) and P = 1.8 x 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DR beta chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;53:1967-1976) | |
| 650 | 7 | a NATURVETENSKAPx Biologi0 (SwePub)1062 hsv//swe |
| 650 | 7 | a NATURAL SCIENCESx Biological Sciences0 (SwePub)1062 hsv//eng |
| 653 | a genome-wide association | |
| 653 | a class-ii alleles | |
| 653 | a ulcerative-colitis | |
| 653 | a t-cells | |
| 653 | a autoimmune hepatitis | |
| 653 | a beta-chain | |
| 653 | a recognition | |
| 653 | a resistance | |
| 653 | a expression | |
| 653 | a haplotypes | |
| 653 | a recognition | |
| 700 | 1 | a Kosmoliaptsis, V.u Addenbrooke's Hospital,University Of Cambridge4 aut |
| 700 | 1 | a Traherne, J. A.u Cambridge Institute for Medical Research4 aut |
| 700 | 1 | a Olsson, Marita,d 1965u Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg4 aut0 (Swepub:cth)marita |
| 700 | 1 | a Boberg, K. M.4 aut |
| 700 | 1 | a Bergquist, A.u Karolinska Institutet4 aut |
| 700 | 1 | a Schrumpf, E.u Universitetet i Oslo,University of Oslo4 aut |
| 700 | 1 | a Bradley, J. A.u University Of Cambridge4 aut |
| 700 | 1 | a Taylor, C. J.u Addenbrooke's Hospital4 aut |
| 700 | 1 | a Lie, B. A.u Oslo universitetssykehus,Oslo University Hospital4 aut |
| 700 | 1 | a Trowsdale, J.u Cambridge Institute for Medical Research4 aut |
| 700 | 1 | a Karlsen, T. H.4 aut |
| 710 | 2 | a Oslo universitetssykehusb Universitetet i Oslo4 org |
| 773 | 0 | t Hepatologyd : Ovid Technologies (Wolters Kluwer Health)g 53:6, s. 1967-1976q 53:6<1967-1976x 0270-9139x 1527-3350 |
| 856 | 4 | u https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.24299 |
| 856 | 4 | u http://dx.doi.org/10.1002/hep.24299y FULLTEXT |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/142715 |
| 856 | 4 8 | u https://doi.org/10.1002/hep.24299 |
| 856 | 4 8 | u https://research.chalmers.se/publication/142715 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:122688149 |
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