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| | <StructureSection load='6jli' size='340' side='right'caption='[[6jli]], [[Resolution|resolution]] 1.78Å' scene=''> | | <StructureSection load='6jli' size='340' side='right'caption='[[6jli]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6jli]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JLI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JLI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6jli]] 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=6JLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JLI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 1.778Å</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=6jli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jli OCA], [http://pdbe.org/6jli PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jli RCSB], [http://www.ebi.ac.uk/pdbsum/6jli PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jli ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6jli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jli OCA], [https://pdbe.org/6jli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jli RCSB], [https://www.ebi.ac.uk/pdbsum/6jli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jli ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLA2R_HUMAN PLA2R_HUMAN]] Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phospholipase sPLA2-IB/PLA2G1B but not sPLA2-IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in proinflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B.<ref>PMID:15611272</ref> <ref>PMID:7721806</ref> | + | [https://www.uniprot.org/uniprot/PLA2R_HUMAN PLA2R_HUMAN] Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phospholipase sPLA2-IB/PLA2G1B but not sPLA2-IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in proinflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B.<ref>PMID:15611272</ref> <ref>PMID:7721806</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cheng, C]] | + | [[Category: Cheng C]] |
| - | [[Category: He, Y]] | + | [[Category: He Y]] |
| - | [[Category: Hu, Z]] | + | [[Category: Hu Z]] |
| - | [[Category: Kong, D]] | + | [[Category: Kong D]] |
| - | [[Category: Yu, B]] | + | [[Category: Yu B]] |
| - | [[Category: Ctld7]]
| + | |
| - | [[Category: Epitope]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Imn]]
| + | |
| - | [[Category: Pla2r]]
| + | |
| Structural highlights
Function
PLA2R_HUMAN Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phospholipase sPLA2-IB/PLA2G1B but not sPLA2-IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in proinflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B.[1] [2]
Publication Abstract from PubMed
M-type phospholipase A2 receptor (PLA2R) is a member of the mannose receptor family. Recent evidence shows that PLA2R is a major autoantigen causing idiopathic membranous nephropathy (IMN), which is an autoimmune disease and one of the most common causes for nephrotic syndrome in adults. The epitope mapping data suggest that the major epitopes of PLA2R locate at the CysR, CTLD1 and CTLD7 domains. However, due to the lack of the high-resolution structural information, it is unclear how the autoantibodies interact with PLA2R. Here we determine the crystal structure of the CTLD7 domain of PLA2R at 1.8A, showing that it adopts a typical CTLD fold, and the structural alignments also provide hints for the potential antibody binding regions. In addition, the high-resolution structural information of CTLD7 could be applied to identify the epitopes for autoantibodies, which would facilitate the therapeutic strategies against IMN.
Crystal structure of the CTLD7 domain of human M-type phospholipase A2 receptor.,Yu B, Hu Z, Kong D, Cheng C, He Y J Struct Biol. 2019 Jul 2. pii: S1047-8477(19)30136-4. doi:, 10.1016/j.jsb.2019.06.007. PMID:31271865[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Granata F, Petraroli A, Boilard E, Bezzine S, Bollinger J, Del Vecchio L, Gelb MH, Lambeau G, Marone G, Triggiani M. Activation of cytokine production by secreted phospholipase A2 in human lung macrophages expressing the M-type receptor. J Immunol. 2005 Jan 1;174(1):464-74. doi: 10.4049/jimmunol.174.1.464. PMID:15611272 doi:http://dx.doi.org/10.4049/jimmunol.174.1.464
- ↑ Ancian P, Lambeau G, Mattei MG, Lazdunski M. The human 180-kDa receptor for secretory phospholipases A2. Molecular cloning, identification of a secreted soluble form, expression, and chromosomal localization. J Biol Chem. 1995 Apr 14;270(15):8963-70. doi: 10.1074/jbc.270.15.8963. PMID:7721806 doi:http://dx.doi.org/10.1074/jbc.270.15.8963
- ↑ Yu B, Hu Z, Kong D, Cheng C, He Y. Crystal structure of the CTLD7 domain of human M-type phospholipase A2 receptor. J Struct Biol. 2019 Jul 2. pii: S1047-8477(19)30136-4. doi:, 10.1016/j.jsb.2019.06.007. PMID:31271865 doi:http://dx.doi.org/10.1016/j.jsb.2019.06.007
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