|
|
| Line 1: |
Line 1: |
| ==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=''> |
| == Introduction ==
| |
| 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 the physiological action of many hormones, neurotransmitters, growth factors, and other extracellular stimuli. These cascades use signaling complexes consisting of G alpha subunits of the Gq family of heterotrimeric guanine nucleotide–binding proteins (G proteins) and PLC-beta isozymes (β1-4). Agonist-stimulated receptors increase exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on Gαq. GTP-bound Gαq engages and 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>
| |
| == Structural highlights ==
| |
| 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>.
| |
| <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.
| |
| PLC- β3 engages Gαq throughout three regions. First, an extended loop between the third and fourth EF hands of PLC- β3 directly buttresses 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 resides primarily within a shallow declivity on the surface of Gαq formed by switch 2 and α3.
| |
|
| |
|
| 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 accelerate the GTP hydrolysis in the GTPase domain.
| |
| <scene name='70/701452/Fig2/1'>TextToBeDisplayed</scene> | | <scene name='70/701452/Fig2/1'>TextToBeDisplayed</scene> |
| <scene name='70/701452/Fig2/4'>TextToBeDisplayed</scene> | | <scene name='70/701452/Fig2/4'>TextToBeDisplayed</scene> |