title: Molecular characterization of the inositol 1,4,5-trisphosphate receptor pore-forming segment.
abstract: Specific residues in the putative pore helix, selectivity filter, and S6 transmembrane helix of the inositol 1,4,5-trisphosphate receptor were mutated in order to examine their effects on channel function. Mutation of 5 of 8 highly conserved residues in the pore helix/selectivity filter region inactivated the channel (C2533A, G2541A, G2545A, G2546A, and G2547A). Of the remaining three mutants, C2527A and R2543A were partially active and G2549A behaved like wild type receptor. Mutation of a putative glycine hinge residue in the S6 helix (G2586A) or a putative gating residue at the cytosolic end of S6 helix (F2592A) had minimal effects on function, although channel function was inactivated by G2586P and F2592D mutations. The mutagenesis data are interpreted in the context of a structural homology model of the inositol 1,4,5-trisphosphate receptor.
authors.affiliation: Department of Pathology and Cell Biology, Thomas Jefferson University, 1020 Locust Drive, Philadelphia, PA 19107, USA.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Schug
authors.forename: Paula C A
authors.initials: PC
authors.lastname: da Fonseca
authors.forename: Cunnigaiper D
authors.initials: CD
authors.lastname: Bhanumathy
authors.forename: Larry
authors.initials: L
authors.lastname: Wagner
authors.forename: Xianchao
authors.initials: X
authors.lastname: Zhang
authors.forename: Bradley
authors.initials: B
authors.lastname: Bailey
authors.forename: Edward P
authors.initials: EP
authors.lastname: Morris
authors.forename: David I
authors.initials: DI
authors.lastname: Yule
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Joseph
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D011994:Recombinant Proteins