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Sci. Signal., 22 May 2012
Vol. 5, Issue 225, p. pe24
[DOI: 10.1126/scisignal.2003148]

PERSPECTIVES

Revisiting Channel Allostery: A Coherent Mechanism in IP3 and Ryanodine Receptors

Kozo Hamada* and Katsuhiko Mikoshiba*

Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Abstract: The inositol 1,4,5-trisphosphate (IP3) receptor is an IP3-gated calcium ion (Ca2+) channel that mediates intracellular IP3-Ca2+ signaling. A fundamental question—how IP3 gates the Ca2+ channel within the IP3 receptor—remains unanswered. A new crystal structure of the N-terminal region of the IP3 receptor reveals allosteric changes by ligand binding and its similarity to the corresponding region of ryanodine receptor. Docking of the crystal structures in the electron microscopy map and an IP3 receptor–ryanodine receptor chimera consistently supported a coherent gating mechanism in these receptors. An intriguing feature was the long distance between the IP3-binding sites and the Ca2+ channel, suggesting that long-range allosteric coupling occurs between these regions upon gating of the channel. These results help integrate previous knowledge on the IP3 and ryanodine receptors and also provide a new framework for understanding the gating mechanism.

* Corresponding authors. E-mail: hamada{at}brain.riken.jp (K.H.); mikosiba{at}brain.riken.jp (K.M.)

Citation: K. Hamada, K. Mikoshiba, Revisiting Channel Allostery: A Coherent Mechanism in IP3 and Ryanodine Receptors. Sci. Signal. 5, pe24 (2012).

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