N-terminus oligomerization is conserved in intracellular calcium release channels

Oligomerization of all three mammalian ryanodine receptor isoforms, a structural requirement for normal intracellular Ca(2+) release channel function, is displayed by the discrete N-terminal domain which assembles into homo- and hetero-tetramers. This is demonstrated in yeast, mammalian cells and native tissue by complementary yeast two-hybrid, chemical cross-linking and co-immunoprecipitation assays. The IP(3) (inositol 1,4,5-trisphosphate) receptor N-terminus (residues 1–667) similarly exhibits tetrameric association as indicated by chemical cross-linking and co-immunoprecipitation assays. The presence of either a 15-residue splice insertion or of the cognate ligand IP(3) did not affect tetramerization of the IP(3) receptor N-terminus. Thus N-terminus tetramerization appears to be an essential intrinsic property that is conserved in both the ryanodine receptor and IP(3) receptor families of mammalian intracellular Ca(2+) release channels.