Figure 1. IP₃ receptor structure and activation.

A. Cryo-electron microscopy image of tetrameric IP₃R1 purified from mouse cerebellum (modified from reference 8). The scale bar =100Å, and the region thought to span the ER membrane and contain the channel pore is indicated by the double lines. Models obtained by other groups are broadly similar to the image shown, but are not identical [1]. B. Model of channel opening; for clarity, only two IP₃R1 subunits are shown (modified from reference 6; see text for description). The domains indicated are the SD (yellow, amino acids 1–223), deletion of which creates a protein that binds IP₃, but which cannot not form functional channels; the LBD (orange and red, amino acids 224–575), which is composed of 2 halves linked by a putative hinge; the channel domain (blue, amino acids 2276–2749), which contains 6 TM helices linked by 3 lumenal loops and 2 cytosolic loops, and a coiled-coil (CC) region that participates in tetramer assembly; and the intervening coupling domain (green, amino acids 576–2275), which contains several regulatory sites. The channel pore is formed by TM helices 5 and 6 and the intervening lumenal loop [2,6,7]. The arrows indicate the putative movements that occur after IP₃ binding that cause channel opening.