6IEJ

The C2 domain of cytosolic phospholipase A2 alpha bound to phosphatidylcholine

Summary for 6IEJ

• Entry DOI: 10.2210/pdb6iej/pdb
• Descriptor: Cytosolic phospholipase A2, CALCIUM ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: lipid binding, phospholipase, calcium binding, c2 domain, hydrolase
• Biological source: Gallus gallus (Chicken)
• Total number of polymer chains: 3
• Total formula weight: 44691.30

Authors

Hirano, Y.,Gao, Y.G.,Stephenson, D.J.,Vu, N.T.,Malinina, L.,Chalfant, C.E.,Patel, D.J.,Brown, R.E. (deposition date: 2018-09-14, release date: 2019-05-22, Last modification date: 2023-11-22)

Primary citation

Hirano, Y.,Gao, Y.G.,Stephenson, D.J.,Vu, N.T.,Malinina, L.,Simanshu, D.K.,Chalfant, C.E.,Patel, D.J.,Brown, R.E.
Structural basis of phosphatidylcholine recognition by the C2-domain of cytosolic phospholipase A2alpha.
Elife, 8:-, 2019

PubMed Abstract: Ca-stimulated translocation of cytosolic phospholipase Aα (cPLAα) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLAα preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report the structure of the cPLAα C2-domain (at 2.2 Å resolution), which contains bound 1,2-dihexanoyl--glycero-3-phosphocholine (DHPC) and Ca ions. Two Ca are complexed at previously reported locations in the lipid-free C2-domain. One of these Caions, along with a third Ca, bridges the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid headgroup recognition via cation-π interaction with the PC trimethylammonium group. Mutagenesis analyses confirm that Tyr96 and Asn65 function in PC binding selectivity by the C2-domain and in the regulation of cPLAα activity. The DHPC-binding mode of the cPLAα C2-domain, which differs from phosphatidylserine or phosphatidylinositol 4,5-bisphosphate binding by other C2-domains, expands and deepens knowledge of the lipid-binding mechanisms mediated by C2-domains.

PubMed: 31050338
DOI: 10.7554/eLife.44760

Experimental method

X-RAY DIFFRACTION (2.206 Å)