抄録
Ligand-gated ion channels, including the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R), are key components in many important signal transduction and amplification pathways. The IP3R forms homotetrameric Ca2+ channels in the endoplasmic reticulum (ER) with an overall mass of 1,252 kDa. Binding of the two co-agonists IP3 and Ca2+ induces the IP3R channel to open, which results in Ca2+ release from the ER into the cytoplasm. This process is crucial for neuronal transmission via Ca2+ signaling and for many other functions that relate to morphological and physiological processes, such as memory and development. We analysed the three-dimensional structure of the ligand-free form of the receptor based on single particle technique1 using an automatic particle picking system, which is capable of identifying particles even in very noisy images of vitrified specimens2. We propose a model which 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 inositol 1,4,5-trisphosphate binding domain. This research is the collaboration with Dr. Fujiyoshi's group and Dr. Mikoshiba's group.
1. C.Sato et al. J. Mol. Biol. 336, 155-164, 2004.
2. T.Ogura and C.Sato. J. Struct. Biol. 145, 63-75, 2004. [Jpn J Physiol 54 Suppl:S9 (2004)]
