DOI: 10.1101/490516Dec 7, 2018Paper

Molecular mechanism of the Orai channel activation

BioRxiv : the Preprint Server for Biology
Xiaofen LiuYuequan SHEN

Abstract

The Orai channel is characterized by voltage independence, low conductance and high Ca2+ selectivity and plays an important role in Ca2+ influx through the plasma membrane. How the channel is activated and promotes Ca2+ permeation are not well understood. Here, we report the crystal structure and cryo-electron microscopy reconstruction of a Drosophila melanogaster Orai mutant (P288L) channel that is constitutively active according to electrophysiology. The open state of the Orai channel showed a hexameric assembly in which six TM1 helices in the center form the ion-conducting pore, and six TM4 helices in the periphery form extended long helices. Orai channel activation requires conformational transduction from TM4 to TM1 and eventually causes the basic section of TM1 to twist outward. The wider pore on the cytosolic side aggregates anions to increase the potential gradient across the membrane and thus facilitate Ca2+ permeation. The open-state structure of the Orai channel offers insights into channel assembly, channel activation and Ca2+ permeation.

Related Concepts

Plasma Membrane
Drosophila
Electrophysiology (Science)
Ion Channel
Peripheral
Structure of Orbital Opening
Channel
Crystal Structure
Health Center
Calcium ion

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