Structural Biochemistry/PLC enzyme

Overview
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PLC, which stands for phosphoinositide-specific phospholipase C, is an enzyme that is linked to common signalling components for most cellular receptors for activation.

Some characteristics of PLC families include:

  • complex
  • modular
  • multi-domain proteins
  • cover broad spectrum for regulatory interactions

PLC enzymes: Functions and Signaling Diversity
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PLC enzymes can be found in eukaryotes. Some of their specific functions and functions of its components include:

  • cleaving the phosphtidylinoitol 4,5-bissphosphate's polar head group using the enzyme's related group of proteins
  • generating 2 second messengers, which are inositol 1,4,5-triphosphate (this i second messenger that is universal in calcium mobilizing) and diacylglycerol (this activates several types of effector proteins). Second messengers helps in regulating a variety of biological functions such as cell motility, sensory transduction, and fertilisation.
  • phosphoinositide species has an important role in targeting specific subcellular compartments. They target components that are important in control of cell movement and membrane trafficking.

PLC enzymes: Structural Elements
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An N-terminal pleckstrin homology domain is part of a conserved core architecture that PLC families share. They also share a C-terminal domain, a TIM barrel that is catalytic, and a series of EF hands. A conserved domain in the PLC isoforms are TIM barrel. They are both functionally and structurally conserved. In other domains, properties in ligand binding can vary. Due to the findings of the core structure from PLC g1, it is revealed that inter-domain interactions are extensive. The domains of EF hands, C2 domain, and TIM barrel probably has similar structures as the N-terminal PH domain of PLCs.

PLC Families
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They have six families consisting of thirteen isoforms in humans. These six families are PLCb, g, d, e, z and h. Compared to other families, PLC b and PLC g have had their regulatory interactions more extensively characterised. In heterotrimeric G proteins, PLC g isoforms has had its regulation through receptor and non-receptor tyrosine kinases distinguished from PLC b isoforms' regulation. It has been found that the Ras Family has small GTPases that directly regulates PLC e. The Rho Family has small GTPases and heterotrimeric G protein subunits can stimulate the enzyme activity of PLC e. This shows that there is an unlikely chance that PLC g isoforms mediates tyrosine kinase linked receptors to stimulate PtdIns(4,5)P2 hydrolysis. Also, it is unlikely that the PLC b isofroms are the only enzymes that activate G protein coupled receptors. There is a possibility that PLC e may also participate in PtdIns(4,5)P2 hydrolysis which tyrosine kinase receptors and GPCRs can trigger.

References
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PLC regulation: emerging pictures for molecular mechanisms. Bunney TD, Katan M. Trends Biochem Sci. 2011 Feb;36(2):88-96. Epub 2010 Oct 1. Review.