Structure of the type 1 inositol 1,4,5-trisphosphate receptor revealed by electron cryomicroscopy

The three- dimensional structure of the type 1 inositol 1,4,5- trisphosphate receptor ( InsP(3)R1) has been determined by electron cryomicroscopy and single- particle reconstruction. The receptor was immunoaffinity- purified and formed functional InsP(3)- and heparin- sensitive channels with a unitary conductance similar to native InsP(3)Rs. The channel structure exhibits the expected 4- fold symmetry and comprises two morphologically distinct regions: a large pinwheel and a smaller square. The pinwheel region has four radial curved spokes interconnected by a central core. The InsP(3)- binding core domain has been localized within each spoke of the pinwheel region by fitting its x- ray structure into our reconstruction. A structural mapping of the amino acid sequences to several functional domains is deduced within the structure of the InsP(3)R1 tetramer.