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| | ==Crystal Structure of MHC class I HLA-A2 molecule complexed with Human Prostaglandin Transporter decapeptide== | | ==Crystal Structure of MHC class I HLA-A2 molecule complexed with Human Prostaglandin Transporter decapeptide== |
| - | <StructureSection load='3mrr' size='340' side='right' caption='[[3mrr]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='3mrr' size='340' side='right'caption='[[3mrr]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mrr]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MRR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MRR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mrr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MRR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MRR FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mr9|3mr9]], [[3mrb|3mrb]], [[3mrc|3mrc]], [[3mrd|3mrd]], [[3mre|3mre]], [[3mrf|3mrf]], [[3mrg|3mrg]], [[3mrh|3mrh]], [[3mri|3mri]], [[3mrj|3mrj]], [[3mrk|3mrk]], [[3mrl|3mrl]], [[3mrm|3mrm]], [[3mrn|3mrn]], [[3mro|3mro]], [[3mrp|3mrp]], [[3mrq|3mrq]], [[3gsn|3gsn]], [[3gso|3gso]], [[3gsq|3gsq]], [[3gsr|3gsr]], [[3gsu|3gsu]], [[3gsv|3gsv]], [[3gsw|3gsw]], [[3gsx|3gsx]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA, HLA-A, HLAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, BETA-2 MICROGLUBULIN, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mrr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mrr OCA], [https://pdbe.org/3mrr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mrr RCSB], [https://www.ebi.ac.uk/pdbsum/3mrr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mrr ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mrr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mrr OCA], [http://pdbe.org/3mrr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mrr RCSB], [http://www.ebi.ac.uk/pdbsum/3mrr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mrr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SO2A1_HUMAN SO2A1_HUMAN]] Defects in SLCO2A1 are the cause of hypertrophic osteoarthropathy, primary, autosomal recessive, type 2 (PHOAR2) [MIM:[http://omim.org/entry/614441 614441]]. PHOAR2 is a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.<ref>PMID:22331663</ref> <ref>PMID:22197487</ref> <ref>PMID:22553128</ref> <ref>PMID:22696055</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | + | [https://www.uniprot.org/uniprot/SO2A1_HUMAN SO2A1_HUMAN] Defects in SLCO2A1 are the cause of hypertrophic osteoarthropathy, primary, autosomal recessive, type 2 (PHOAR2) [MIM:[https://omim.org/entry/614441 614441]. PHOAR2 is a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.<ref>PMID:22331663</ref> <ref>PMID:22197487</ref> <ref>PMID:22553128</ref> <ref>PMID:22696055</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/SO2A1_HUMAN SO2A1_HUMAN]] May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | + | [https://www.uniprot.org/uniprot/SO2A1_HUMAN SO2A1_HUMAN] May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| - | *[[Major histocompatibility complex|Major histocompatibility complex]]
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bonneville, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Chouquet, A]] | + | [[Category: Bonneville M]] |
| - | [[Category: Debeaupuis, E]] | + | [[Category: Chouquet A]] |
| - | [[Category: Echasserieau, K]] | + | [[Category: Debeaupuis E]] |
| - | [[Category: Housset, D]] | + | [[Category: Echasserieau K]] |
| - | [[Category: Legoux, F]] | + | [[Category: Housset D]] |
| - | [[Category: Machillot, P]] | + | [[Category: Legoux F]] |
| - | [[Category: Reiser, J B]] | + | [[Category: Machillot P]] |
| - | [[Category: Saulquin, X]] | + | [[Category: Reiser J-B]] |
| - | [[Category: Decapeptide]]
| + | [[Category: Saulquin X]] |
| - | [[Category: Hla]]
| + | |
| - | [[Category: Immune response]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Mart1 analogue]]
| + | |
| - | [[Category: Melan-a analogue]]
| + | |
| - | [[Category: Mhc class i]]
| + | |
| - | [[Category: Prostaglandin transporter]]
| + | |
| - | [[Category: Self peptide]]
| + | |
| - | [[Category: Tumoral peptide]]
| + | |
| Structural highlights
Disease
SO2A1_HUMAN Defects in SLCO2A1 are the cause of hypertrophic osteoarthropathy, primary, autosomal recessive, type 2 (PHOAR2) [MIM:614441. PHOAR2 is a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.[1] [2] [3] [4]
Function
SO2A1_HUMAN May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A.
Publication Abstract from PubMed
The structural rules governing peptide/MHC (pMHC) recognition by T cells remain unclear. To address this question, we performed a structural characterization of several HLA-A2/peptide complexes and assessed in parallel their antigenicity, by analyzing the frequency of the corresponding Ag-specific naive T cells in A2(+) and A2(-) individuals, as well as within CD4(+) and CD8(+) subsets. We were able to find a correlation between specific naive T cell frequency and peptide solvent accessibility and/or mobility for a subset of moderately prominent peptides. However, one single structural parameter of the pMHC complexes could not be identified to explain each peptide antigenicity. Enhanced pMHC antigenicity was associated with both highly biased TRAV usage, possibly reflecting favored interaction between particular pMHC complexes and germline TRAV loops, and peptide structural features allowing interactions with a broad range of permissive CDR3 loops. In this context of constrained TCR docking mode, an optimal peptide solvent exposed surface leading to an optimal complementarity with TCR interface may constitute one of the key features leading to high frequency of specific T cells. Altogether our results suggest that frequency of specific T cells depends on the fine-tuning of several parameters, the structural determinants governing TCR-pMHC interaction being just one of them.
Analysis of relationships between peptide/MHC structural features and naive T cell frequency in humans.,Reiser JB, Legoux F, Gras S, Trudel E, Chouquet A, Leger A, Le Gorrec M, Machillot P, Bonneville M, Saulquin X, Housset D J Immunol. 2014 Dec 15;193(12):5816-26. doi: 10.4049/jimmunol.1303084. Epub 2014 , Nov 12. PMID:25392532[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Seifert W, Kuhnisch J, Tuysuz B, Specker C, Brouwers A, Horn D. Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing. Hum Mutat. 2012 Apr;33(4):660-4. doi: 10.1002/humu.22042. Epub 2012 Feb 24. PMID:22331663 doi:10.1002/humu.22042
- ↑ Zhang Z, Xia W, He J, Zhang Z, Ke Y, Yue H, Wang C, Zhang H, Gu J, Hu W, Fu W, Hu Y, Li M, Liu Y. Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am J Hum Genet. 2012 Jan 13;90(1):125-32. doi: 10.1016/j.ajhg.2011.11.019. Epub, 2011 Dec 22. PMID:22197487 doi:10.1016/j.ajhg.2011.11.019
- ↑ Diggle CP, Parry DA, Logan CV, Laissue P, Rivera C, Restrepo CM, Fonseca DJ, Morgan JE, Allanore Y, Fontenay M, Wipff J, Varret M, Gibault L, Dalantaeva N, Korbonits M, Zhou B, Yuan G, Harifi G, Cefle K, Palanduz S, Akoglu H, Zwijnenburg PJ, Lichtenbelt KD, Aubry-Rozier B, Superti-Furga A, Dallapiccola B, Accadia M, Brancati F, Sheridan EG, Taylor GR, Carr IM, Johnson CA, Markham AF, Bonthron DT. Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis. Hum Mutat. 2012 Aug;33(8):1175-81. doi: 10.1002/humu.22111. Epub 2012 May 29. PMID:22553128 doi:10.1002/humu.22111
- ↑ Busch J, Frank V, Bachmann N, Otsuka A, Oji V, Metze D, Shah K, Danda S, Watzer B, Traupe H, Bolz HJ, Kabashima K, Bergmann C. Mutations in the prostaglandin transporter SLCO2A1 cause primary hypertrophic osteoarthropathy with digital clubbing. J Invest Dermatol. 2012 Oct;132(10):2473-6. doi: 10.1038/jid.2012.146. Epub 2012 , Jun 14. PMID:22696055 doi:10.1038/jid.2012.146
- ↑ Reiser JB, Legoux F, Gras S, Trudel E, Chouquet A, Leger A, Le Gorrec M, Machillot P, Bonneville M, Saulquin X, Housset D. Analysis of relationships between peptide/MHC structural features and naive T cell frequency in humans. J Immunol. 2014 Dec 15;193(12):5816-26. doi: 10.4049/jimmunol.1303084. Epub 2014 , Nov 12. PMID:25392532 doi:http://dx.doi.org/10.4049/jimmunol.1303084
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