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The remote allosteric control of Orai channel gating
- Source :
- PLoS Biology, Vol 17, Iss 8, p e3000413 (2019), PLoS Biology
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- The Orai channel is characterized by voltage independence, low conductance, and high Ca2+ selectivity and plays an important role in Ca2+ influx through the plasma membrane (PM). How the channel is activated and promotes Ca2+ permeation is not well understood. Here, we report the crystal structure and cryo-electron microscopy (cryo-EM) reconstruction of a Drosophila melanogaster Orai (dOrai) mutant (P288L) channel that is constitutively active according to electrophysiology. The open state of the Orai channel showed a hexameric assembly in which 6 transmembrane 1 (TM1) helices in the center form the ion-conducting pore, and 6 TM4 helices in the periphery form extended long helices. Orai channel activation requires conformational transduction from TM4 to TM1 and eventually causes the basic section of TM1 to twist outward. The wider pore on the cytosolic side aggregates anions to increase the potential gradient across the membrane and thus facilitate Ca2+ permeation. The open-state structure of the Orai channel offers insights into channel assembly, channel activation, and Ca2+ permeation.<br />The structure of a constitutively active mutant of the fruit fly Orai calcium influx channel reveals a conformational transduction pathway upon channel activation and suggests an anion-assisted mechanism for calcium permeation.
- Subjects :
- 0301 basic medicine
ORAI1 Protein
Gating
Physical Chemistry
Biochemistry
Fluorophotometry
Spectrum Analysis Techniques
Single Channel Recording
0302 clinical medicine
Fluorescence Resonance Energy Transfer
Electron Microscopy
Biology (General)
Membrane Electrophysiology
Calcium signaling
Microscopy
Crystallography
Physics
Drosophila Melanogaster
General Neuroscience
Eukaryota
Animal Models
Condensed Matter Physics
Lipids
Insects
Chemistry
Bioassays and Physiological Analysis
Experimental Organism Systems
Spectrophotometry
Physical Sciences
Crystal Structure
Drosophila
General Agricultural and Biological Sciences
Research Article
Anions
Arthropoda
QH301-705.5
Allosteric regulation
Biology
Research and Analysis Methods
Green Fluorescent Protein
General Biochemistry, Genetics and Molecular Biology
Protein–protein interaction
03 medical and health sciences
Model Organisms
Solid State Physics
Animals
Secretion
Calcium Signaling
Stromal Interaction Molecule 1
Ion channel
Ions
General Immunology and Microbiology
Endoplasmic reticulum
Electrophysiological Techniques
Organisms
Biology and Life Sciences
Proteins
Electron Cryo-Microscopy
Invertebrates
Luminescent Proteins
030104 developmental biology
Membrane protein
Animal Studies
Biophysics
Calcium
Calcium Channels
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15457885 and 15449173
- Volume :
- 17
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS Biology
- Accession number :
- edsair.doi.dedup.....3d2529dff35e1aa548a6ac47e111f9bc