7KR5

Cryo-EM structure of the CRAC channel Orai in an open conformation; H206A gain-of-function mutation in complex with an antibody

Summary for 7KR5

• Entry DOI: 10.2210/pdb7kr5/pdb
• EMDB information: 23002
• Descriptor: Calcium release-activated calcium channel protein 1, 19B5 Fab heavy chain, 19B5 Fab light chain, ... (4 entities in total)
• Functional Keywords: ion channel, calcium, soce, crac, eukaryotic, open structure, membrane protein, amphiboles, cryo-em, transport protein-immune system complex, transport protein/immune system
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 12
• Total formula weight: 302422.40

Authors

Long, S.B.,Hou, X.,Outhwaite, I.R. (deposition date: 2020-11-18, release date: 2020-12-09, Last modification date: 2025-05-21)

Primary citation

Hou, X.,Outhwaite, I.R.,Pedi, L.,Long, S.B.
Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.
Elife, 9:-, 2020

PubMed Abstract: 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.

PubMed: 33252040
DOI: 10.7554/eLife.62772

Experimental method

ELECTRON MICROSCOPY (3.3 Å)