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| | ==Structure of paired immunoglobulin-like type 2 receptor (PILR )== | | ==Structure of paired immunoglobulin-like type 2 receptor (PILR )== |
| - | <StructureSection load='4nfb' size='340' side='right' caption='[[4nfb]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='4nfb' size='340' side='right'caption='[[4nfb]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nfb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NFB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NFB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4nfb]] is a 1 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=4NFB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NFB FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qfo|1qfo]], [[1o7v|1o7v]], [[2zg2|2zg2]], [[4nfd|4nfd]], [[4nfc|4nfc]]</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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nfb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nfb RCSB], [http://www.ebi.ac.uk/pdbsum/4nfb PDBsum]</span></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=4nfb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nfb OCA], [https://pdbe.org/4nfb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nfb RCSB], [https://www.ebi.ac.uk/pdbsum/4nfb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nfb ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/PILRA_HUMAN PILRA_HUMAN] Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRA is thought to act as a cellular signaling inhibitory receptor by recruiting cytoplasmic phosphatases like PTPN6/SHP-1 and PTPN11/SHP-2 via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules. Receptor for PIANP.<ref>PMID:10903717</ref> <ref>PMID:18358807</ref> <ref>PMID:21241660</ref> |
| - | Paired immunoglobulin-like type 2 receptor alpha (PILRalpha) and beta (PILRbeta) belong to the PILR family and are related to innate immune regulation in various species. Despite their high sequence identity, PILRalpha and PILRbeta are shown to have variant sialic acid (SA) binding avidities. To explore the molecular basis of this interaction, we solved the crystal structures of PILRalpha and PILRbeta at resolutions of 1.6 A and 2.2 A, respectively. Both molecules adopt a typical siglec fold but use a hydrophobic bond to substitute the siglec-specific disulfide linkage for protein stabilization. We further used HSV-1 glycoprotein B (gB) as a representative molecule to study the PILR-SA interaction. Deploying site-directed mutagenesis, we demonstrated that three residues (Y2, R95, and W108) presented on the surface of PILRalpha form the SA binding site equivalent to those in siglecs but are arranged in a unique linear mode. PILRbeta differs from PILRalpha in one of these three residues (L108), explaining its inability to engage gB. Mutation of L108 to tryptophan in PILRbeta restored the gB-binding capacity. We further solved the structure of this PILRbeta mutant complexed with SA, which reveals the atomic details mediating PILR/SA recognition. In comparison with the free PILR structures, amino acid Y2 oriented variantly in the complex structure, thereby disrupting the linear arrangement of PILR residues Y2, R95, and W108. In conclusion, our study provides significant implications for the PILR-SA interaction and paves the way for understanding PILR-related ligand binding. | + | |
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| - | PILRalpha and PILRbeta have a siglec fold and provide the basis of binding to sialic acid.,Lu Q, Lu G, Qi J, Wang H, Xuan Y, Wang Q, Li Y, Zhang Y, Zheng C, Fan Z, Yan J, Gao GF Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8221-6. doi:, 10.1073/pnas.1320716111. Epub 2014 May 19. PMID:24843130<ref>PMID:24843130</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fan, Z.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Gao, G.]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, Y.]] | + | [[Category: Fan Z]] |
| - | [[Category: Lu, G.]] | + | [[Category: Gao G]] |
| - | [[Category: Lu, Q.]] | + | [[Category: Li Y]] |
| - | [[Category: Qi, J.]] | + | [[Category: Lu G]] |
| - | [[Category: Wang, H.]] | + | [[Category: Lu Q]] |
| - | [[Category: Yan, J.]] | + | [[Category: Qi J]] |
| - | [[Category: Zhang, Y.]] | + | [[Category: Wang H]] |
| - | [[Category: Cell surface]]
| + | [[Category: Yan J]] |
| - | [[Category: Hsv-1 gb]]
| + | [[Category: Zhang Y]] |
| - | [[Category: Igv-like]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immune-related inhibition receptor]]
| + | |
| Structural highlights
Function
PILRA_HUMAN Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRA is thought to act as a cellular signaling inhibitory receptor by recruiting cytoplasmic phosphatases like PTPN6/SHP-1 and PTPN11/SHP-2 via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules. Receptor for PIANP.[1] [2] [3]
References
- ↑ Fournier N, Chalus L, Durand I, Garcia E, Pin JJ, Churakova T, Patel S, Zlot C, Gorman D, Zurawski S, Abrams J, Bates EE, Garrone P. FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells. J Immunol. 2000 Aug 1;165(3):1197-209. PMID:10903717
- ↑ Satoh T, Arii J, Suenaga T, Wang J, Kogure A, Uehori J, Arase N, Shiratori I, Tanaka S, Kawaguchi Y, Spear PG, Lanier LL, Arase H. PILRalpha is a herpes simplex virus-1 entry coreceptor that associates with glycoprotein B. Cell. 2008 Mar 21;132(6):935-44. PMID:18358807 doi:http://dx.doi.org/S0092-8674(08)00205-5
- ↑ Kogure A, Shiratori I, Wang J, Lanier LL, Arase H. PANP is a novel O-glycosylated PILRalpha ligand expressed in neural tissues. Biochem Biophys Res Commun. 2011 Feb 18;405(3):428-33. doi:, 10.1016/j.bbrc.2011.01.047. Epub 2011 Jan 15. PMID:21241660 doi:http://dx.doi.org/10.1016/j.bbrc.2011.01.047
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