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Science 338 (6112): 1308-1313

Copyright © 2012 by the American Association for the Advancement of Science

Crystal Structure of the Calcium Release–Activated Calcium Channel Orai

Xiaowei Hou, Leanne Pedi, Melinda M. Diver, Stephen B. Long*

Abstract: The plasma membrane protein Orai forms the pore of the calcium release–activated calcium (CRAC) channel and generates sustained cytosolic calcium signals when triggered by depletion of calcium from the endoplasmic reticulum. The crystal structure of Orai from Drosophila melanogaster, determined at 3.35 angstrom resolution, reveals that the calcium channel is composed of a hexameric assembly of Orai subunits arranged around a central ion pore. The pore traverses the membrane and extends into the cytosol. A ring of glutamate residues on its extracellular side forms the selectivity filter. A basic region near the intracellular side can bind anions that may stabilize the closed state. The architecture of the channel differs markedly from other ion channels and gives insight into the principles of selective calcium permeation and gating.

Structural Biology Program, Memorial Sloan-Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY 10065, USA.

* To whom correspondence should be addressed. E-mail: longs{at}mskcc.org

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