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 (IP(3)R) is a tetrameric intracellular Ca(2+) channel, which mediates the release of Ca(2+) from the endoplasmic reticulum in response to many different extracellular stimuli. We present a 3D structure of the type 1 IP(3)R obtained by electron microscopy and single-particle analysis that reveals its domain organization. The IP(3)R 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 IP(3)R 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.
da Fonseca
Paula C A
PC
Biomedical Sciences Division, Sir Alexander Fleming Building, Imperial College of Science Technology and Medicine, London SW7 2AZ, United Kingdom.
Morris
Stephen A
SA
Nerou
Edmund P
EP
Taylor
Colin W
CW
Morris
Edward P
EP
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*; D002462:Cell Membrane / Q000737:chemistry; D002531:Cerebellum / Q000737:chemistry; D003593:Cytoplasm / Q000648:ultrastructure; D007091:Image Processing, Computer-Assisted; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels / Q000737:chemistry / Q000302:isolation & purification; D008854:Microscopy, Electron; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000302:isolation & purification; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear