7kr5

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

Structural highlights

7kr5 is a 12 chain structure with sequence from Drosophila melanogaster and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.3Å
Ligands:CA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ORAI1_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 PubMed

The 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.

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Citations
13 reviews cite this structure
Relevance of Membrane Contact Sites in Cancer Progression.
Gil-Hernández et al. (2020)
12 more
10 other articles
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See Also

References

  1. ↑ Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006 May 11;441(7090):179-85. Epub 2006 Apr 2. PMID:16582901 doi:http://dx.doi.org/nature04702
  2. ↑ Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 2006 May 26;312(5777):1220-3. Epub 2006 Apr 27. PMID:16645049 doi:http://dx.doi.org/10.1126/science.1127883
  3. ↑ Prakriya M, Feske S, Gwack Y, Srikanth S, Rao A, Hogan PG. Orai1 is an essential pore subunit of the CRAC channel. Nature. 2006 Sep 14;443(7108):230-3. PMID:16921383 doi:10.1038/nature05122
  4. ↑ Hou X, Pedi L, Diver MM, Long SB. Crystal structure of the calcium release-activated calcium channel Orai. Science. 2012 Dec 7;338(6112):1308-13. doi: 10.1126/science.1228757. Epub 2012, Nov 22. PMID:23180775 doi:http://dx.doi.org/10.1126/science.1228757
  5. ↑ Hou X, Outhwaite IR, Pedi L, Long SB. Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation. Elife. 2020 Nov 30;9:e62772. PMID:33252040 doi:10.7554/eLife.62772

Contents


PDB ID 7kr5

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