Structures reveal opening of the store-operated calcium channel Orai Journal Article

Authors: Hou, X.; Burstein, S. R.; Long, S. B.
Article Title: Structures reveal opening of the store-operated calcium channel Orai
Abstract: The store-operated calcium (Ca2+) channel Orai governs Ca2+ influx through the plasma membrane of many non-excitable cells in metazoans. The channel opens in response to the depletion of Ca2+ stored in the endoplasmic reticulum (ER). Loss- and gain-of-function mutants of Orai cause disease. Our previous work revealed the structure of Orai with a closed pore. Here, using a gain-of-function mutation that constitutively activates the channel, we present an X-ray structure of Drosophila melanogaster Orai in an open conformation. Well-defined electron density maps reveal that the pore is dramatically dilated on its cytosolic side in comparison to the slender closed pore. Cations and anions bind in different regions of the open pore, informing mechanisms for ion permeation and Ca2+ selectivity. Opening of the pore requires the release of cytosolic latches. Together with additional Xray structures of an unlatched-but-closed conformation, we propose a sequence for store-operated activation. © 2018, eLife Sciences Publications Ltd. All rights reseved.
Journal Title: eLife
Volume: 7
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd.  
Date Published: 2018-08-30
Start Page: e36758
Language: English
DOI: 10.7554/eLife.36758
PUBMED: 30160233
PROVIDER: scopus
PMCID: PMC6170153
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Xiaowei Hou
    6 Hou
  2. Stephen Barstow Long
    26 Long