PLC beta 3 Gq: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Shir Navot (talk | contribs) No edit summary |
Shir Navot (talk | contribs) No edit summary |
||
| Line 4: | Line 4: | ||
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> | 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 == | == 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 switch regions I-III. | 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 and a C2 domain. | <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 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 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. | ||
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. 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. 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. | ||
<scene name='70/701452/Fig2/1'>TextToBeDisplayed</scene> | <scene name='70/701452/Fig2/1'>TextToBeDisplayed</scene> | ||
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
