Phospholipase membrane binding

Lambeau G, Barhanin J, Schweitz H, Qar J, Lazdunski M (1989) Identification and properties of very high affinity brain membrane-binding sites for a neurotoxic phospholipase from the taipan venom. J Biol Chem 264 11503-510... 

Tatulian SA, Biltonen RL, Tamm LK. Structural changes in a secretory phospholipase A2 induced by membrane binding a clue to interfacial activation J. Mol. Biol. 1997 268 809-815. 

During recent years, groups interested in the role of Ca in secretion and in the control of membrane cytoskeleton have identified some intracellular phospholipid-binding proteins that appear to be distinct from the calmodulin superfamily these include lipocortin, endonexin, calelectrin, p36, and calpac-tin These membrane-binding proteins are collectively called annexins, and contain repeated domains distinct from EF-hands. The Ca sites are very similar to that observed in phospholipase A2, as shown by the recently determined x-ray structure of annexin A condensed overview of the interaction of Ca + with intracellular proteins is shown in Figure 3.16. We will now go on to discuss the molecular properties of some of the proteins mentioned above, starting with calmodulin. 

Cells are composed of different intracellular compartments embedded in the cytoplasm, and are bounded by the plasma membrane. One of this compartments, the endoplasmic reticulum (ER), acts as intracellular store for Ca + ions. In a resting cell the Ca + concentration in the cytoplasm ([Ca +]c) is kept low ( 100 nM) and in the ER high ( 20 M) by active transport through the ER and plasma membrane. Binding of agonist to its receptor at the plasma membrane activates phospholipase C (PLC). This enzyme is responsible for the production of the second messenger IP3, which can freely diffuse in the cytoplasm. IP3 activates Ca " " channels... 

Figure 10. The G-protein cascades in smooth muscle catalyze the exchange GDP for GTP on G-protein. Following the binding of GTP, the trimeric G-protein splits into an a-GTP part and a P-y part. The a-GTP part ordinarily then combines with its specific apoenzyme to constitute the active enzyme. For the activation of the contractile activation path, the enzyme is phospholipase C and the second messenger products are IP3 and DAG. The IP3 in the myoplasm binds to Ca channels in the SR membrane, opening them. Other second messengers include the inhibitors of contractile activity, cGMP and cAMP.

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

Inositol triphosphate (IP3)-gated channels are also associated with membrane-bound receptors for hormones and neurotransmitters. In this case, binding of a given substance to its receptor causes activation of another membrane-bound protein, phospholipase C. This enzyme promotes hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to IP3. The IP3 then diffuses to the sarcoplasmic reticulum and opens its calcium channels to release Ca++ ions from this intracellular storage site. 

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