View source for 7qsr


==CryoEM structure of the Ectodomain of Human PLA2R==
<StructureSection load='7qsr' size='340' side='right'caption='[[7qsr]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qsr]] 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=7QSR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QSR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <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=7qsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qsr OCA], [https://pdbe.org/7qsr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qsr RCSB], [https://www.ebi.ac.uk/pdbsum/7qsr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qsr ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Membranous nephropathy is an autoimmune kidney disease caused by autoantibodies targeting antigens present on glomerular podocytes, instigating a cascade leading to glomerular injury. The most prevalent circulating autoantibodies in membranous nephropathy are against phospholipase A2 receptor (PLA2R), a cell surface receptor. The dominant epitope in PLA2R is located within the cysteine-rich domain, yet high-resolution structure-based mapping is lacking. In this study, we define the key nonredundant amino acids in the dominant epitope of PLA2R involved in autoantibody binding. We further describe two essential regions within the dominant epitope and spacer requirements for a synthetic peptide of the epitope for drug discovery. In addition, using cryo-electron microscopy, we have determined the high-resolution structure of PLA2R to 3.4 A resolution, which shows that the dominant epitope and key residues within the cysteine-rich domain are accessible at the cell surface. In addition, the structure of PLA2R not only suggests a different orientation of domains but also implicates a unique immunogenic signature in PLA2R responsible for inducing autoantibody formation and recognition.

Structure of PLA2R reveals presentation of the dominant membranous nephropathy epitope and an immunogenic patch.,Fresquet M, Lockhart-Cairns MP, Rhoden SJ, Jowitt TA, Briggs DC, Baldock C, Brenchley PE, Lennon R Proc Natl Acad Sci U S A. 2022 Jul 19;119(29):e2202209119. doi: , 10.1073/pnas.2202209119. Epub 2022 Jul 11. PMID:35858348<ref>PMID:35858348</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qsr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baldock C]]
[[Category: Briggs DC]]
[[Category: Lockhart-Cairns MP]]