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TitleCryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateNov 30, 2020
AuthorsXiaowei Hou / Ian R Outhwaite / Leanne Pedi / Stephen Barstow Long /
PubMed AbstractThe calcium release-activated calcium channel Orai regulates Ca entry into non-excitable cells and is required for proper immune function. While the channel typically opens following Ca release from ...The calcium release-activated calcium channel Orai regulates Ca entry into non-excitable cells and is required for proper immune function. While the channel typically opens following Ca release from the endoplasmic reticulum, certain pathologic mutations render the channel constitutively open. Previously, using one such mutation (H206A), we obtained low (6.7 Å) resolution X-ray structural information on Orai in an open conformation (Hou et al., 2018). Here we present a structure of this open conformation at 3.3 Å 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.
External linksElife / PubMed:33252040 / PubMed Central
MethodsEM (single particle)
Resolution3.3 Å
Structure data

23002

7kr5

EMDB-23002, PDB-7kr5:
Cryo-EM structure of the CRAC channel Orai in an open conformation; H206A gain-of-function mutation in complex with an antibody
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • drosophila melanogaster (fruit fly)
  • mus musculus (house mouse)
KeywordsTRANSPORT PROTEIN/IMMUNE SYSTEM / ion channel / calcium / SOCE / CRAC / eukaryotic / open structure / MEMBRANE PROTEIN / amphiboles / cryo-EM / TRANSPORT PROTEIN-IMMUNE SYSTEM complex

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