Domain organization of the type 1 inositol 1,4,5-trisphosphate receptor as revealed by single-particle analysis

The inositol 1,4,5-trisphosphate receptor (IP3R) is a tetrameric intracellular Ca2+ channel, which mediates the release of Ca2+ from the endoplasmic reticulum in response to many different extracellular stimuli. We present a 3D structure of the type 1 IP3R obtained by electron microscopy and single-particle analysis that reveals its domain organization. The IP3R has a flower-like appearance with fourfold symmetry and is made up of three distinct domains connected by slender links. By relating the organization of the structural domains to secondary-structure predictions and biochemical data we develop a model in which structural domains are mapped onto the amino acid sequence to deduce the location of the channel region and the cytoplasmic inositol 1,4,5-trisphosphate-binding and modulatory subdomains. The structure of the IP3R is compared with that of other tetrameric cation channels. The channel domain is similar in size and shape to its counterparts in the ryanodine receptor and the Shaker voltage-gated K+ channel.