The phospholipid bilayer of biological membranes is first and foremost a means of demarcating aqueous compartments by establishing a hydrophobic barrier that restricts the permeability of water-soluble compounds. One of the many additional functions of phospholipids is to provide the fatty acid substrates that can be converted into important signalling messengers, such as leukotrienes and prostaglandins. In order to cleave the linkage between the hydrophobic fatty acid and the hydrophilic headgroup, the enzyme phospholipase A2 (PLA2) attaches itself to membranes via its C2 domain, which contains binding sites for two calcium ions.
Starting from structural and biophysical constraints, Jaud et al. have carried out a molecular dynamics simulation of the interaction between the PLA2 C2 domain and a phosphatidyl choline bilayer. They find that the neighboring lipids reorganize to form a crater-like indentation, with the alkyl chains lining the bottom and the polar headgroups around the rim. Into this depression fit the three calcium-binding loops (CBLs) and the two complexed Ca2+ ions, whose primary role seems to be to mask the negatively charged loops rather than to coordinate directly to the phosphoryl oxygens, from which they are insulated by a layer of water molecules. — GJC
Biophys. J. 91, 10.1529/biophysj.106.090704 (2006).