Inositol 1,4,5-Trisphosphate Receptor

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Shannon King

Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. Andrea Gorrell.

spinqualitylabelsall models Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca²⁺ signalling processes in a variety of organisms ^[1]

Overall Structure

The specific type of inositol 1,4,5-trisphosphate receptor (InsP₃R) protein discussed here is the mouse type one InsP₃R, also called InsP₃R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP₃) binding region, the central modulatory region, and the carboxy-terminus channel region.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 receptor site for InsP₃.^[1] The overall structure with the ligand bound can be seen here:

Image:1n4k1.PNG

Domain Structure

The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.^[1] In the case of the InsP₃R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP₃R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.^[1]

The α-domain of InsP₃R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.^[1] In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.^[1] Within the α-domain of mouse InsP₃R1, there are two large, highly conserved surfaces.^[1] Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.^[1] A possible option for this kind of binding domain would be the InsP₃ binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP₃ ligand.^[1]

The structures of the two domains can be seen in the image below. Image:Fold regions.PNG

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