Structure and function of phosphatidylserine-specific phospholipase A₁

Phospholipase A₁ (PLA₁) is an enzyme that hydrolyzes the sn-1 fatty acids from phospholipids and produces 2-acyl-lysophospholipids. Although PLA₁ activities are detected in many tissues and cell lines, a limited number of PLA₁s have been purified and cloned so far. These include phosphatidylserine (PS)-specific PLA₁ (PS-PLA₁) from rat platelets, PLA₁ from vespid venom, and phosphatidic acid (PA)-preferential PLA₁ (PA-PLA₁). Structurally, the former two PLA₁s belong to the lipase family, where they form a subfamily among the lipase family. An alignment of the PLA₁s with other members of the lipase family revealed two molecular characteristics of PLA₁: the presence of extremely short lids and deleted β9 loops. The two surface loops have been implicated in the ligand recognition in human pancreatic lipase (PL) and guinea pig PL-related protein 2. Under physiological conditions, accessibility of PS-PLA₁ to its substrate is limited as it is a secreted enzyme and PS is normally located in the inner leaflet of the lipid bilayer. However, PS-PLA₁ efficiently hydrolyzes PS exposed on the surface of cells such as apoptotic cells and activated platelets, and produces 2-acyl-lysophosphatidylserine (lysoPS), which is a lipid mediator for mast cells, T cells and neural cells. Identification of PS-PLA₁ reveals the presence of PLA₁ subfamily within the lipase family and suggests that PLA₁ has a role in the production of lysophospholipid mediators.