Revisiting channel allostery: A coherent mechanism in IP3 and ryanodine receptors

Kozo Hamada*, Katsuhiko Mikoshiba

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)


The inositol 1,4,5-trisphosphate (IP3) receptor is an IP 3-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 IP 3 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.

Original languageEnglish
Article numberpe24
JournalScience Signaling
Issue number225
Publication statusPublished - 22 May 2012
Externally publishedYes


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