IP3 Receptor Plasticity Underlying Diverse Functions

In the body, extracellular stimuli produce inositol 1,4,5-trisphosphate (IP 3 ), an intracellular chemical signal that binds to the IP 3 receptor (IP 3 R) to release calcium ions (Ca 2+ ) from the endoplasmic reticulum. In the past 40 years, the wide-ranging functions mediated by IP 3 R and its genetic defects causing a variety of disorders have been unveiled. Recent cryo-electron microscopy and X-ray crystallography have resolved IP 3 R structures and begun to integrate with concurrent functional studies, which can explicate IP 3 -dependent opening of Ca 2+ -conducting gates placed ∼90 Å away from IP 3 -binding sites and its regulation by Ca 2+ . This review highlights recent research progress on the IP 3 R structure and function. We also propose how protein plasticity within IP 3 R, which involves allosteric gating and assembly transformations accompanied by rapid and chronic structural changes, would enable it to regulate diverse functions at cellular microdomains in pathophysiological states.