Three-dimensional structure of the type 1 inositol 1,4,5-trisphosphate receptor at 24 Å resolution

We report here the first three-dimensional structure of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R). From cryo-electron microscopic images of purified receptors embedded in vitreous ice, a three-dimensional structure was determined by use of standard single particle reconstruction techniques. The structure is strikingly different from that of the ryanodine receptor at similar resolution despite molecular similarities between these two calcium release channels. The 24 Angstrom resolution structure of the IP3R takes the shape of an uneven dumbbell, and is similar to170 Angstrom tall. Its larger end is bulky, with four arms protruding laterally by similar to50 Angstrom and, in comparison with the receptor topology, probably corresponds to the cytoplasmic domain of the receptor. The lateral dimension at the height of the protruding arms is similar to155 Angstrom. The smaller end, whose lateral dimension is similar to100 Angstrom, has structural features indicative of the membrane-spanning domain. A central opening in this domain, which is occluded on the cytoplasmic half, outlines a pathway for calcium flow in the open state of the channel.