TY - JOUR
T1 - IP3 Receptor Plasticity Underlying Diverse Functions
AU - Hamada, Kozo
AU - Mikoshiba, Katsuhiko
N1 - Publisher Copyright:
© 2020 Annual Reviews Inc.. All rights reserved.
PY - 2020
Y1 - 2020
N2 - In the body, extracellular stimuli produce inositol 1,4,5-trisphosphate (IP3), an intracellular chemical signal that binds to the IP3 receptor (IP3R) to release calcium ions (Ca2+) from the endoplasmic reticulum. In the past 40 years, the wide-ranging functions mediated by IP3R and its genetic defects causing a variety of disorders have been unveiled. Recent cryo-electron microscopy and X-ray crystallography have resolved IP3R structures and begun to integrate with concurrent functional studies, which can explicate IP3-dependent opening of Ca2+-conducting gates placed ∼90 Å away from IP3-binding sites and its regulation by Ca2+. This review highlights recent research progress on the IP3R structure and function. We also propose how protein plasticity within IP3R, 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.
AB - In the body, extracellular stimuli produce inositol 1,4,5-trisphosphate (IP3), an intracellular chemical signal that binds to the IP3 receptor (IP3R) to release calcium ions (Ca2+) from the endoplasmic reticulum. In the past 40 years, the wide-ranging functions mediated by IP3R and its genetic defects causing a variety of disorders have been unveiled. Recent cryo-electron microscopy and X-ray crystallography have resolved IP3R structures and begun to integrate with concurrent functional studies, which can explicate IP3-dependent opening of Ca2+-conducting gates placed ∼90 Å away from IP3-binding sites and its regulation by Ca2+. This review highlights recent research progress on the IP3R structure and function. We also propose how protein plasticity within IP3R, 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.
KW - 4-5-trisphosphate
KW - 4-5-trisphosphate receptor
KW - Ca channel
KW - allosteric regulation
KW - endoplasmic reticulum
KW - gating mechanism
KW - inositol 1
KW - inositol 1
UR - http://www.scopus.com/inward/record.url?scp=85079251080&partnerID=8YFLogxK
U2 - 10.1146/annurev-physiol-021119-034433
DO - 10.1146/annurev-physiol-021119-034433
M3 - Review article
C2 - 31730387
AN - SCOPUS:85079251080
SN - 0066-4278
VL - 82
SP - 151
EP - 176
JO - Annual Review of Physiology
JF - Annual Review of Physiology
ER -