Inositol 1,4,5-trisphosphate receptor contains multiple cavities and L-shaped ligand-binding domains.
Calcium concentrations are strictly regulated in all biological cells, and one of the key molecules responsible for this regulation is the inositol 1,4,5-trisphosphate receptor, which was known to form a homotetrameric Ca(2+) channel in the endoplasmic reticulum. The receptor is involved in neuronal transmission via Ca(2+) signaling and for many other functions that relate to morphological and physiological processes in living organisms. We analysed the three-dimensional structure of the ligand-free form of the receptor based on a single-particle technique using an originally developed electron microscope equipped with a helium-cooled specimen stage and an automatic particle picking system. We propose a model that explains the complex mechanism for the regulation of Ca(2+) release by co-agonists, Ca(2+), inositol 1,4,5-trisphosphate based on the structure of multiple internal cavities and a porous balloon-shaped cytoplasmic domain containing a prominent L-shaped density which was assigned by the X-ray structure of the inositol 1,4,5-trisphosphate binding domain.
Sato
Chikara
C
Neuroscience Research Institute and Biological Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), Umezono 1-1-4, Tsukuba 305-8568, Japan.
Hamada
Kozo
K
Ogura
Toshihiko
T
Miyazawa
Atsuo
A
Iwasaki
Kenji
K
Hiroaki
Yoko
Y
Tani
Kazutoshi
K
Terauchi
Akiko
A
Fujiyoshi
Yoshinori
Y
Mikoshiba
Katsuhiko
K
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium