title: Flexible architecture of IP3R1 by Cryo-EM.
abstract: Inositol 1,4,5-trisphosphate receptors (IP3Rs) play a fundamental role in generating Ca2+ signals that trigger many cellular processes in virtually all eukaryotic cells. Thus far, the three-dimensional (3D) structure of these channels has remained extremely controversial. Here, we report a subnanometer resolution electron cryomicroscopy (cryo-EM) structure of a fully functional type 1 IP3R from cerebellum in the closed state. The transmembrane region reveals a twisted bundle of four α helices, one from each subunit, that form a funnel shaped structure around the 4-fold symmetry axis, strikingly similar to the ion-conduction pore of K+ channels. The lumenal face of IP3R1 has prominent densities that surround the pore entrance and similar to the highly structured turrets of Kir channels. 3D statistical analysis of the cryo-EM density map identifies high variance in the cytoplasmic region. This structural variation could be attributed to genuine structural flexibility of IP3R1.
authors.affiliation: National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ludtke
authors.forename: Thao P
authors.initials: TP
authors.lastname: Tran
authors.forename: Que T
authors.initials: QT
authors.lastname: Ngo
authors.forename: Vera Yu
authors.initials: VY
authors.lastname: Moiseenkova-Bell
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
authors.forename: Irina I
authors.initials: II
authors.lastname: Serysheva
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry; D002531:Cerebellum / Q000378:metabolism; D020285:Cryoelectron Microscopy; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D007295:Inositol Phosphates / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D013499:Surface Properties
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D008081:Liposomes; D002118:Calcium