Three-dimensional structure of recombinant type 1 inositol 1,4,5-trisphosphate receptor

IP(3)Rs (inositol 1,4,5-trisphosphate receptors) are the intracellular channels that mediate release of Ca(2+) from the endoplasmic reticulum in response to the many stimuli that evoke Ins(1,4,5)P(3) formation. We characterized and purified type 1 IP(3)R heterologously expressed in Sf9 insect cells, and used the purified IP(3)R1 to determine its three-dimensional structure by electron microscopy and single-particle analysis. Recombinant IP(3)R1 has 4-fold symmetry with overall dimensions of approx. 19.5 nm×19.5 nm×17.5 nm. It comprises a small domain, which is likely to include the pore, linked by slender bridges to a large cytoplasmic domain with four petal-like regions. Our structures of recombinant IP(3)R1 and native cerebellar IP(3)R have similar appearances and dimensions. The only notable difference is the absence of a central stigma-like domain from the cytoplasmic region of recombinant IP(3)R1. The first structure of a recombinant IP(3)R is an important step towards developing three-dimensional structures of IP(3)R that better contribute to our understanding of the structural basis of IP(3)R activation.