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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 ? 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.

SUBMITTER: Ludtke SJ

PROVIDER: S-EPMC3154621 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Flexible architecture of IP3R1 by Cryo-EM.

Ludtke Steven J SJ Tran Thao P TP Ngo Que T QT Moiseenkova-Bell Vera Yu VY Chiu Wah W Serysheva Irina I II

Structure (London, England : 1993) 20110801 8

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, o ...[more]

PMID: 21827954

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