مرکز منطقه ای اطلاع رساني علوم و فناوري - Increasing molecular diversity of secreted phospholipases A2 and their receptors and binding proteins

Latin Abstract :

Secreted phospholipases A2 (sPLA2s) form a large family of structurally related enzymes which are widespread in nature. Snake venoms are known for decades to contain a tremendous molecular diversity of sPLA2s which can exert a myriad of toxic and pharmacological effects. Recent studies indicate that mammalian cells also express a variety of sPLA2s with ten distinct members identified so far, in addition to the various other intracellular PLA2s. Furthermore, scanning of nucleic acid databases fueled by the different genome projects indicates that several sPLA2s are also present in invertebrate animals like Drosophila melanogaster as well as in plants. All of these sPLA2s catalyze the hydrolysis of glycerophospholipids at the sn-2 position to release free fatty acids and lysophospholipids, and thus could be important for the biosynthesis of biologically active lipid mediators. However, the recent identification of a variety of membrane and soluble proteins that bind to sPLA2s suggests that the sPLA2 enzymes could also function as high affinity ligands. So far, most of the binding data have been accumulated with venom sPLA2s and group IB and IIA mammalian sPLA2s. Collectively, venom sPLA2s have been shown to bind to membrane and soluble mammalian proteins of the C-type lectin superfamily (M-type sPLA2 receptor and lung surfactant proteins), to pentraxin and reticulocalbin proteins, to factor Xa and to N-type receptors. Venom sPLA2s also associate with three distinct types of sPLA2 inhibitors purified from snake serum that belong to the C-type lectin superfamily, to the three-finger protein superfamily and to proteins containing leucine-rich repeats. On the other hand, mammalian group IB and IIA sPLA2s can bind to the M-type receptor, and group IIA sPLA2s can associate with lung surfactant proteins, factor Xa and proteoglycans including glypican and decorin, a mammalian protein containing a leucine-rich repeat.