Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor

Mol Cell. 2005 Jan 21;17(2):193-203. doi: 10.1016/j.molcel.2004.11.047.

Abstract

Binding of inositol 1,4,5-trisphosphate (IP(3)) to the amino-terminal region of IP(3) receptor promotes Ca(2+) release from the endoplasmic reticulum. Within the amino terminus, the first 220 residues directly preceding the IP(3) binding core domain play a key role in IP(3) binding suppression and regulatory protein interaction. Here we present a crystal structure of the suppressor domain of the mouse type 1 IP(3) receptor at 1.8 A. Displaying a shape akin to a hammer, the suppressor region contains a Head subdomain forming the beta-trefoil fold and an Arm subdomain possessing a helix-turn-helix structure. The conserved region on the Head subdomain appeared to interact with the IP(3) binding core domain and is in close proximity to the previously proposed binding sites of Homer, RACK1, calmodulin, and CaBP1. The present study sheds light onto the mechanism underlying the receptor's sensitivity to the ligand and its communication with cellular signaling proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Channels / chemistry*
  • Calcium Channels / metabolism
  • Crystallography, X-Ray
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Folding
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Ryanodine Receptor Calcium Release Channel / chemistry
  • Sequence Alignment

Substances

  • Calcium Channels
  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Ryanodine Receptor Calcium Release Channel

Associated data

  • PDB/1XZZ