6bbf | pdb_00006bbf
The CRAC channel Orai in an open conformation; H206A gain-of-function mutation
Structural highlights
FunctionCRCM1_DROME Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores. Regulates transcription factor NFAT nuclear import.[1] [2] Publication Abstract from PubMedThe store-operated calcium (Ca(2+)) channel Orai governs Ca(2+) influx through the plasma membrane of many non-excitable cells in metazoans. The channel opens in response to the depletion of Ca(2+) 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 Ca(2+) selectivity. Opening of the pore requires the release of cytosolic latches. Together with additional X-ray structures of an unlatched-but-closed conformation, we propose a sequence for store-operated activation. Structures reveal opening of the store-operated calcium channel Orai.,Hou X, Burstein SR, Long SB Elife. 2018 Aug 30;7. pii: 36758. doi: 10.7554/eLife.36758. PMID:30160233[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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