6iej
The C2 domain of cytosolic phospholipase A2 alpha bound to phosphatidylcholineThe C2 domain of cytosolic phospholipase A2 alpha bound to phosphatidylcholine
Structural highlights
FunctionPublication Abstract from PubMedCa(2+)-stimulated translocation of cytosolic phospholipase A2alpha (cPLA2alpha) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLA2alpha preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report cPLA2alpha C2-domain structure (2.2A resolution) containing bound 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) and Ca(2+) ions. Two Ca(2+) are complexed at locations previously reported for lipid-free C2-domain. One of these Ca(2+) along with a third Ca(2+) bridge the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid headgroup recognition via cation-pi interaction with the PC trimethylammonium group. Mutagenesis analyses confirm Tyr96 and Asn65 function in PC binding selectivity by C2-domain and regulation of cPLA2alpha activity. The differing DHPC-binding mode of cPLA2alpha C2-domain, compared to phosphatidylserine or phosphatidylinositol 4,5-bisphosphate binding by other C2-domains, expands and deepens knowledge of lipid-binding mechanisms mediated by C2-domains. Structural basis of phosphatidylcholine recognition by the C2-domain of cytosolic phospholipase A2alpha.,Hirano Y, Gao YG, Stephenson DJ, Vu NT, Malinina L, Simanshu DK, Chalfant CE, Patel DJ, Brown RE Elife. 2019 May 3;8. pii: 44760. doi: 10.7554/eLife.44760. PMID:31050338[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||