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.

Subscribe

Sci. Signal., 19 March 2013
Vol. 6, Issue 267, p. pe9
[DOI: 10.1126/scisignal.2003971]

PERSPECTIVES

Orai Channel Pore Properties and Gating by STIM: Implications from the Orai Crystal Structure

Brad S. Rothberg, Youjun Wang, and Donald L. Gill*

Department of Biochemistry, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.

Abstract: The Orai channels are unusual, yet prominent, calcium (Ca2+) signal mediators in most cell types. Orai proteins are structurally unique, having little sequence homology with other ion channels. They are also functionally unique with exceedingly high selectivity for Ca2+, mediating both short-term Ca2+ homeostasis and long-term Ca2+ signals important for transcriptional control. Operating in the plasma membrane (PM), Orai channel regulation is unprecedented among ion channels; channel gating occurs through an elaborate intermembrane coupling with stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER). STIM proteins function as sensors of Ca2+ stored in the ER lumen and translocate into ER-PM junctions to tether and activate Orai channels when ER Ca2+ concentration decreases. Crystallization studies reveal an unexpected hexameric structure for the Orai channel and provide important insights into the pore architecture, the structural basis of its unusual cation selectivity, and how channel gating occurs through its coupling with STIM proteins.

* Corresponding author. E-mail: dgill{at}temple.edu

Citation: B. S. Rothberg, Y. Wang, D. L. Gill, Orai Channel Pore Properties and Gating by STIM: Implications from the Orai Crystal Structure. Sci. Signal. 6, pe9 (2013).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Pore waters regulate ion permeation in a calcium release-activated calcium channel.
H. Dong, G. Fiorin, V. Carnevale, W. Treptow, and M. L. Klein (2013)
PNAS 110, 17332-17337
   Abstract »    Full Text »    PDF »
The Extended Transmembrane Orai1 N-terminal (ETON) Region Combines Binding Interface and Gate for Orai1 Activation by STIM1.
I. Derler, P. Plenk, M. Fahrner, M. Muik, I. Jardin, R. Schindl, H. J. Gruber, K. Groschner, and C. Romanin (2013)
J. Biol. Chem. 288, 29025-29034
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


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