6jli
From Proteopedia
Crystal structure of CTLD7 domain of human PLA2R
Structural highlights
FunctionPLA2R_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 PubMedM-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
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Categories: Homo sapiens | Large Structures | Cheng C | He Y | Hu Z | Kong D | Yu B
