Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


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


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} (K.H.); mikosiba{at} (K.M.)

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

Read the Full Text

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882