A Hybrid Approach of Cryo-Electron Microscopy and X-ray Crystallography Proposes the Structure and Ca²⁺ Mobilization Mechanism of Inositol 1,4,5-Trisphosphate Receptor

Abstract

A hybrid approach using X-ray crystallography and cryo-electron microscopy provides opportunities to reveal the activation mechanism and pathway of biological macromolecules with large conformational changes. Structural analysis of the Ca²⁺ release channel, inositol 1,4,5-trisphosphate receptor (IP₃R) is a good example to introduce this powerful approach. Docking of the atomic coordinate of the fragment including binding domain of inositol 1,4,5-trisphosphate (IP₃) and Ca²⁺ into the three-dimensional density map of the type 1 IP₃R reconstructed from cryo-electron micrographs leads to proposing a novel regulation mechanism of Ca²⁺ mobilization.