7kr5
Cryo-EM structure of the CRAC channel Orai in an open conformation; H206A gain-of-function mutation in complex with an antibody
Structural highlights
FunctionORAI1_DROME Pore-forming subunit of inward rectifying Ca(2+) release-activated Ca(2+) (CRAC) channels. Assembles in hexameric CRAC channels that mediate Ca(2+) influx upon depletion of endoplasmic reticulum Ca(2+) store and channel activation by Ca(2+) sensor Stim, a process known as store-operated Ca(2+) entry (SOCE). Regulates transcription factor NFAT nuclear import.[1] [2] [3] [4] Publication Abstract from PubMedThe calcium release-activated calcium channel Orai regulates Ca(2+) entry into non-excitable cells and is required for proper immune function. While the channel typically opens following Ca(2+) release from the endoplasmic reticulum, certain pathologic mutations render the channel constitutively open. Previously, using one such mutation (H206A), we obtained low (6.7 A) resolution X-ray structural information on Drosophila melanogaster Orai in an open conformation (Hou et al., 2018). Here we present a structure of this open conformation at 3.3 A resolution using fiducial-assisted cryo-electron microscopy. The improved structure reveals the conformations of amino acids in the open pore, which dilates by outward movements of subunits. A ring of phenylalanine residues repositions to expose previously shielded glycine residues to the pore without significant rotational movement of the associated helices. Together with other hydrophobic amino acids, the phenylalanines act as the channel's gate. Structured M1-M2 turrets, not evident previously, form the channel's extracellular entrance. Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.,Hou X, Outhwaite IR, Pedi L, Long SB Elife. 2020 Nov 30;9:e62772. doi: 10.7554/eLife.62772. PMID:33252040[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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