Work

Crystal Structure of the Calcium Release–Activated Calcium Channel Orai

Year: 2012

Type: article

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.

Source: Science

DOI: 10.1126/science.1228757

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

Institution: Memorial Sloan Kettering Cancer Center

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of General Medical Sciences

Awards: 3D Structure and Function of CRAC Channels, Cancer Center Support Grant