PLC beta 3 Gq

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==Unique bidirectional interactions of Phospholipase C beta 3 with G alpha Q==
==Unique bidirectional interactions of Phospholipase C beta 3 with G alpha Q==
<StructureSection load='3ohm' size='340' side='right' caption='Caption for this structure' scene=''>
<StructureSection load='3ohm' size='340' side='right' caption='Caption for this structure' scene=''>
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== Introduction ==
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Phospholipase C (PLC) catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate [IP2] to the second messengers inositol 1,4,5-trisphosphate [IP3] and diacylglycerol [DAG] in an essential step for many physiological cascades. When the receptor is stimulated by ligand of some kind it increase exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on Gαq. GTP-bound Gαq activates PLC- β3, and PLC- β3 increases up to three orders of magnitude the rate of hydrolysis of GTP by its activating G protein. This is a unique mechanism when the PLC-β3 enzyme has the ability to terminate the Gαq protein signal in addition to being activated by it.<ref>PMID:20966218</ref> <ref>PMID:23880553</ref>
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== Structural highlights ==
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The Gαq subunit consists two domains, one is the GTPase domain and the other is the alpha helical domain. These domains include three regions called <scene name='70/701452/Fig2/2'>switch regions I-III</scene>.
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<scene name='70/701452/Fig1/9'>The PLC- β3 has several domains</scene> consisting of N-terminal PH domain, a series of four EF hands, a catalytic TIM barrel that the X/Y linker connect its two halves and a C2 domain.<ref>PMID:20966218</ref>
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PLC- β3 engages Gαq throughout three regions. First, an extended loop between the third and fourth EF hands of PLC- β3 directly supports switch residues critical for GTP hydrolysis by Gαq. Second, the region of PLC- β3 that connects the catalytic TIM barrel and the C2 domain interacts with both switches 1 and 2 of Gαq. Third, a segment composed of a helix-turn-helix at the C terminus of the C2 domain mostly located within a shallow declivity on the surface of Gαq formed by switch 2 and α3.<ref>PMID:20966218</ref>
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PLC-β3 interacts with a surface on Gαq that overlaps almost completely with portions of Gα subunits needed for engagement of RGS proteins and the effector-binding region. Other effectors are known to engage the effector-binding site within Gα subunits. There are a large family of regulator of G protein signaling (RGS) proteins that independently accelerates the GTP hydrolysis in the GTPase domain. <ref>PMID:20966218</ref>
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<scene name='70/701452/Fig2/1'>TextToBeDisplayed</scene>
<scene name='70/701452/Fig2/1'>TextToBeDisplayed</scene>

Revision as of 08:13, 7 May 2015

Unique bidirectional interactions of Phospholipase C beta 3 with G alpha Q

Caption for this structure

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References

  1. Waldo GL, Ricks TK, Hicks SN, Cheever ML, Kawano T, Tsuboi K, Wang X, Montell C, Kozasa T, Sondek J, Harden TK. Kinetic Scaffolding Mediated by a Phospholipase C-{beta} and Gq Signaling Complex. Science. 2010 Nov 12;330(6006):974-80. Epub 2010 Oct 21. PMID:20966218 doi:10.1126/science.1193438
  2. Lyon AM, Tesmer JJ. Structural insights into phospholipase C-beta function. Mol Pharmacol. 2013 Oct;84(4):488-500. doi: 10.1124/mol.113.087403. Epub 2013 Jul, 23. PMID:23880553 doi:http://dx.doi.org/10.1124/mol.113.087403
  3. Waldo GL, Ricks TK, Hicks SN, Cheever ML, Kawano T, Tsuboi K, Wang X, Montell C, Kozasa T, Sondek J, Harden TK. Kinetic Scaffolding Mediated by a Phospholipase C-{beta} and Gq Signaling Complex. Science. 2010 Nov 12;330(6006):974-80. Epub 2010 Oct 21. PMID:20966218 doi:10.1126/science.1193438
  4. Waldo GL, Ricks TK, Hicks SN, Cheever ML, Kawano T, Tsuboi K, Wang X, Montell C, Kozasa T, Sondek J, Harden TK. Kinetic Scaffolding Mediated by a Phospholipase C-{beta} and Gq Signaling Complex. Science. 2010 Nov 12;330(6006):974-80. Epub 2010 Oct 21. PMID:20966218 doi:10.1126/science.1193438
  5. Waldo GL, Ricks TK, Hicks SN, Cheever ML, Kawano T, Tsuboi K, Wang X, Montell C, Kozasa T, Sondek J, Harden TK. Kinetic Scaffolding Mediated by a Phospholipase C-{beta} and Gq Signaling Complex. Science. 2010 Nov 12;330(6006):974-80. Epub 2010 Oct 21. PMID:20966218 doi:10.1126/science.1193438

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