Ca2+ signalling processes: 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='38/382942/Cv/1'> | <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'> | ||
*[[Inositol 1,4,5-Trisphosphate Receptor]] | *[[Inositol 1,4,5-Trisphosphate Receptor]] | ||
[[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>. The specific type of inositol 1,4,5-trisphosphate receptor (InsP<sub>3</sub>R) protein discussed here is the mouse type 1 InsP<sub>3</sub>R, also called InsP<sub>3</sub>R1. This polypeptide contains three major regions: the <scene name='38/382942/N_terminal_domain/1'>amino terminal</scene> inositol 1,4,5-trisphosphate (InsP<sub>3</sub>) binding region, the central modulatory region, and the <scene name='38/382942/C_terminal_domain/1'>carboxy-terminus channel region</scene>.<ref name="mainpaper"/> The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.<ref name="mainpaper"/> The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.<ref name="mainpaper"/> The C-terminal end is quite different, consisting of a bundle made of eight α-helices.<ref name="mainpaper"/> The interface of the two domains is lined with basic residues and forms the <scene name='38/382942/Ip3_binding_pocket/1'>receptor site</scene> for InsP<sub>3</sub>.<ref name="mainpaper"/> The InsP<sub>3</sub>R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.<ref name="functionref"/> | [[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>. The specific type of inositol 1,4,5-trisphosphate receptor (InsP<sub>3</sub>R) protein discussed here is the mouse type 1 InsP<sub>3</sub>R, also called InsP<sub>3</sub>R1. This polypeptide contains three major regions: the <scene name='38/382942/N_terminal_domain/1'>amino terminal</scene> inositol 1,4,5-trisphosphate (InsP<sub>3</sub>) binding region, the central modulatory region, and the <scene name='38/382942/C_terminal_domain/1'>carboxy-terminus channel region</scene>.<ref name="mainpaper"/> The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.<ref name="mainpaper"/> The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.<ref name="mainpaper"/> The C-terminal end is quite different, consisting of a bundle made of eight α-helices.<ref name="mainpaper"/> The interface of the two domains is lined with basic residues and forms the <scene name='38/382942/Ip3_binding_pocket/1'>receptor site</scene> for InsP<sub>3</sub>.<ref name="mainpaper"/> The InsP<sub>3</sub>R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.<ref name="functionref"/> 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. | ||
*[[Calcium-dependent protein kinase]] | *[[Calcium-dependent protein kinase]] | ||
*[[Calcium/Calmodulin-dependent protein kinase]] | *[[Calcium/Calmodulin-dependent protein kinase]] | ||
Revision as of 17:52, 13 December 2021
Inositol 1,4,5-Trisphosphate Receptor binding protein is a ubiquitous protein involved in the Ca2+ signalling processes in a variety of organisms [1]. The specific type of inositol 1,4,5-trisphosphate receptor (InsP3R) protein discussed here is the mouse type 1 InsP3R, also called InsP3R1. This polypeptide contains three major regions: the inositol 1,4,5-trisphosphate (InsP3) binding region, the central modulatory region, and the .[1] The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.[1] The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.[1] The C-terminal end is quite different, consisting of a bundle made of eight α-helices.[1] The interface of the two domains is lined with basic residues and forms the for InsP3.[1] The InsP3R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.[2] The InsP3 sits between the two domains of the protein. Highly are present on both domains and are responsible for the binding of InsP3 to InsP3R.[1] Since the InsP3 ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP3-binding domain.[2] In binding, water molecules are involved in hydrogen bonding between InsP3 and its receptor as well as interactions between protein side chains and phosphorous.[1] (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 InsP3 play a small role in binding to InsP3.[1] 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.[1] The non-basic residues T266, T267, G268, and Y567 are also integral in InsP3 coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.[1] In all likelihood, the InsP3-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.[2] 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 InsP3 ligand.
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ReferencesReferences
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, Tong KI, Yoshikawa F, Furuichi T, Iwai M, Michikawa T, Mikoshiba K, Ikura M. Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature. 2002 Dec 12;420(6916):696-700. Epub 2002 Nov 17. PMID:12442173 doi:10.1038/nature01268
- ↑ 2.0 2.1 2.2 Cite error: Invalid
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