The inositol trisphosphate receptor is a membrane glycoprotein complex acting as a calcium regulator for the cell. This is important for various cell activities and is implicated in neural plasticity. Using single-particle analysis and a helium-stage-equipped electron microscope, we created a three-dimensional model which illuminates the mechanism for the regulation of calcium release by the combined action of Ca2+ and inositol 1,4,5-triphosphate.

Abstract from: Journal of Molecular Biology, Volume 336, Issue 1, 6 February 2004, Pages 155-164


Inositol 1,4,5-trisphosphate Receptor Contains Multiple Cavities and L-shaped Ligand-binding Domains>

Chikara Sato(1), Kozo Hamada(2, 6), Toshihiko Ogura(1), Atsuo Miyazawa(3), Kenji Iwasaki(4), Yoko Hiroaki(5), Kazutoshi Tani(5), Akiko Terauchi(6), Yoshinori Fujiyoshi(3, 5, 7), and Katsuhiko Mikoshiba(2, 6, 8)

(1) 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 (2) Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan (3) RIKEN Harima Institute, 1-1-1 Koto, Mikazuki-cho, Sayo, Hyogo 679-5148, Japan (4) Research Center for Ultra-High Voltage Electron Microscopy, Osaka University, 7-1, Mihogaoka, Ibaraki, Osaka 567-0047, Japan (5) Department of Biophysics, Faculty of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan (6) Calcium Oscillation Project, International Cooperative Research Project (ICORP), Japan Science and Technology Agency (JST), 3-14-4, Shirokanedai, Minato-ku, Tokyo 108-0071, Japan (7) Japan Biological Information Research Centre, 2-41-6 Aomi, Koto-ku, Tokyo 135-0064, Japan (8) Division of Molecular Neurobiology, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

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 Ca2+ channel in the endoplasmic reticulum. The receptor is involved in neuronal transmission via Ca2+ 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 Ca2+ release by co-agonists, Ca2+, 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.

PubMed Link

We investigate the structure of proteins and molecular complexes at the macromolecular level, using a combination of Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Optical Microscopy (OM).