Inositol 1,4,5-Trisphosphate Receptor: Difference between revisions
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<StructureSection load='1n4K' size='350' side='right' caption='Mouse inositol triphosphate receptor ligand-binding core complex with its ligand inositol triphosphate (PDB entry [[1n4k]])' scene=''> | <StructureSection load='1n4K' size='350' side='right' caption='Mouse inositol triphosphate receptor ligand-binding core complex with its ligand inositol triphosphate (PDB entry [[1n4k]])' scene='38/382942/Cv/1'> | ||
==Introduction== | ==Introduction== | ||
[[Inositol 1,4,5-Trisphosphate Receptor]] binding protein is a ubiquitous protein involved in the Ca<sup>2+</sup> signalling processes in a variety of organisms <ref name="mainpaper">PMID:12442173</ref> | [[Inositol 1,4,5-Trisphosphate Receptor]] binding protein is a ubiquitous protein involved in the Ca<sup>2+</sup> signalling processes in a variety of organisms <ref name="mainpaper">PMID:12442173</ref>. See also [[Endoplasmic reticulum/Sarcoplasmic reticulum receptors]], [[Receptor]] and [[Ca2+ signalling processes]]. | ||
==Structure== | ==Structure== | ||
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=== Binding the InsP<sub>3</sub> Ligand: Mechanism and Structural Components=== | === Binding the InsP<sub>3</sub> Ligand: Mechanism and Structural Components=== | ||
The InsP<sub>3</sub> <scene name='Sandbox_170/1n4k/8'>ligand</scene> sits between the two domains of the protein. Highly <scene name='38/382942/Ip3_binding_pocket/1'>basic amino acid residues</scene> are present on both domains and are responsible for the binding of InsP<sub>3</sub> to InsP<sub>3</sub>R.<ref name="mainpaper"/> Since the InsP<sub>3</sub> ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP<sub>3</sub>-binding domain.<ref name="functionref"/> In binding, water molecules are involved in hydrogen bonding between InsP<sub>3</sub> and its receptor as well as interactions between protein side chains and phosphorous.<ref name="mainpaper"/> | The InsP<sub>3</sub> <scene name='Sandbox_170/1n4k/8'>ligand</scene> sits between the two domains of the protein. Highly <scene name='38/382942/Ip3_binding_pocket/1'>basic amino acid residues</scene> are present on both domains and are responsible for the binding of InsP<sub>3</sub> to InsP<sub>3</sub>R.<ref name="mainpaper"/> Since the InsP<sub>3</sub> ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP<sub>3</sub>-binding domain.<ref name="functionref"/> In binding, water molecules are involved in hydrogen bonding between InsP<sub>3</sub> and its receptor as well as interactions between protein side chains and phosphorous.<ref name="mainpaper"/> <scene name='38/382942/Cv/4'>Active site</scene> (water molecules shown as red spheres). Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP<sub>3</sub> play a small role in binding to InsP<sub>3</sub>.<ref name="mainpaper"/> Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.<ref name="mainpaper"/> The non-basic residues T266, T267, G268, and Y567 are also integral in InsP<sub>3</sub> coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.<ref name="mainpaper"/> In all likelihood, the InsP<sub>3</sub>-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.<ref name="functionref"/> This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP<sub>3</sub> ligand. | ||
[[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]] | [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]] | ||
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
[[3jrr]] – mInsP3R III ligand-binding suppressor domain | [[6dqj]], [[6dr2]], [[6dra]], [[6uqk]] – hInsP3R III – human - Cryo EM<br /> | ||
[[6dqn]], [[6dqs]], [[6dqv]], [[6dqz]], [[6dr0]], [[6drc]] – hInsP3R III + IP3 - Cryo EM<br /> | |||
[[5x9z]], [[5xa0]] – mInsP3R I - mouse<br /> | |||
[[3jrr]] – mInsP3R III ligand-binding suppressor domain <br /> | |||
[[1xzz]] - mInsP3R I ligand-binding suppressor domain<br /> | [[1xzz]] - mInsP3R I ligand-binding suppressor domain<br /> | ||
[[1n4k]] - mInsP3R I receptor-binding core + | [[1n4k]] - mInsP3R I receptor-binding core + IP3<br /> | ||
[[5gug]], [[5xa1]] – mInsP3R I + IP3<br /> | |||
[[3t8s]], [[3uj4]] - rInsP3R I ligand-binding domain - rat<br /> | [[3t8s]], [[3uj4]] - rInsP3R I ligand-binding domain - rat<br /> | ||
[[3uj0]] - rInsP3R I ligand-binding domain + | [[3uj0]] - rInsP3R I ligand-binding domain + IP3<br /> | ||
[[3jav]], [[6mu2]] – rInsP3R I – Cryo EM<br /> | |||
[[7lhe]], [[7lhf]] – rInsP3R I + lipid – Cryo EM<br /> | |||
[[6mu1]] – rInsP3R I + adenophostin – Cryo EM<br /> | |||
==References== | ==References== | ||