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An autoinhibitory helix in the C-terminal region of phospholipase C-? mediates G?q activation.

ABSTRACT: The enzyme phospholipase C-? (PLC?) is a crucial regulator of intracellular calcium levels whose activity is controlled by heptahelical receptors that couple to members of the Gq family of heterotrimeric G proteins. We have determined atomic structures of two invertebrate homologs of PLC? (PLC21) from cephalopod retina and identified a helix from the C-terminal regulatory region that interacts with a conserved surface of the catalytic core of the enzyme. Mutations designed to disrupt the analogous interaction in human PLC?3 considerably increase basal activity and diminish stimulation by G?q. G?q binding requires displacement of the autoinhibitory helix from the catalytic core, thus providing an allosteric mechanism for activation of PLC?.

SUBMITTER: Lyon AM

PROVIDER: S-EPMC3168981 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation.

Lyon Angeline M AM Tesmer Valerie M VM Dhamsania Vishan D VD Thal David M DM Gutierrez Joanne J Chowdhury Shoaib S Suddala Krishna C KC Northup John K JK Tesmer John J G JJ

Nature structural & molecular biology 20110807 9

The enzyme phospholipase C-β (PLCβ) is a crucial regulator of intracellular calcium levels whose activity is controlled by heptahelical receptors that couple to members of the Gq family of heterotrimeric G proteins. We have determined atomic structures of two invertebrate homologs of PLCβ (PLC21) from cephalopod retina and identified a helix from the C-terminal regulatory region that interacts with a conserved surface of the catalytic core of the enzyme. Mutations designed to disrupt the analogo ...[more]

PMID: 21822282

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