IP₃-mediated gating mechanism of the IP₃ receptor revealed by mutagenesis and X-ray crystallography.

ABSTRACT: The inositol 1,4,5-trisphosphate (IP₃) receptor (IP₃R) is an IP₃-gated ion channel that releases calcium ions (Ca²⁺) from the endoplasmic reticulum. The IP₃-binding sites in the large cytosolic domain are distant from the Ca²⁺ conducting pore, and the allosteric mechanism of how IP₃ opens the Ca²⁺ channel remains elusive. Here, we identify a long-range gating mechanism uncovered by channel mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type 1 IP₃R in the absence and presence of IP₃ Analyses of two distinct space group crystals uncovered an IP₃-dependent global translocation of the curvature α-helical domain interfacing with the cytosolic and

SUBMITTER: Hamada K 

PROVIDER: S-EPMC5422816 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature