Flexible architecture of IP3R1 by Cryo-EM

Structure. 2011 Aug 10;19(8):1192-9. doi: 10.1016/j.str.2011.05.003.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / chemistry
  • Cerebellum / metabolism
  • Cryoelectron Microscopy*
  • Inositol 1,4,5-Trisphosphate Receptors / chemistry*
  • Inositol 1,4,5-Trisphosphate Receptors / isolation & purification
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Inositol Phosphates / chemistry
  • Liposomes / chemistry
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rats
  • Surface Properties


  • Inositol 1,4,5-Trisphosphate Receptors
  • Inositol Phosphates
  • Liposomes
  • Calcium