ArticleProceedings of the National Academy of Sciences of the United States of America2013
Pore waters regulate ion permeation in a calcium release-activated calcium channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 71 citations in OpenAlex.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- Preorganized Electric Fields in Voltage-Gated Sodium Channels.Chembiochem : a European journal of chemical biology · 2025Article
- Water in peripheral TM-interfaces of Orai1-channels triggers pore opening.Communications biology · 2024Article
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- Determinants of conductance of a bacterial voltage-gated sodium channel.Biophysical journal · 2021Article
- Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
- The Orai Pore Opening Mechanism.International journal of molecular sciences · 2021Review
- The Impact of Mutation L138F/L210F on the Orai Channel: A Molecular Dynamics Simulation Study.Frontiers in molecular biosciences · 2021Article
- Unveiling the Gating Mechanism of CRAC Channel: A Computational Study.Frontiers in molecular biosciences · 2021Article
- Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.eLife · 2020Article
- Blockage of Store-Operated CaCancers · 2020Article
- Molecular basis of allosteric Orai1 channel activation by STIM1.The Journal of physiology · 2020Review
- The basic residues in the Orai1 channel inner pore promote opening of the outer hydrophobic gate.The Journal of general physiology · 2020Article
- Toward a Model for Activation of Orai Channel.iScience · 2019Article
- Structural features of STIM and Orai underlying store-operated calcium entry.Current opinion in cell biology · 2019Review
- STIM1 activation of Orai1.Cell calcium · 2019Review
- Role of the Interaction Motif in Maintaining the Open Gate of an Open Sodium Channel.Biophysical journal · 2018Article
- Binding of the general anesthetic sevoflurane to ion channels.PLoS computational biology · 2018Article
- Mapping the functional anatomy of Orai1 transmembrane domains for CRAC channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recent crystal structure of Orai, the pore unit of a calcium release-activated calcium (CRAC) channel, is used as the starting point for molecular dynamics and free-energy calculations designed to probe this channel's conduction properties. In free molecular dynamics simulations, cations localize preferentially at the extracellular channel entrance near the ring of Glu residues identified in the crystal structure, whereas anions localize in the basic intracellular half of the pore. To begin to understand ion permeation, the potential of mean force (PMF) was calculated for displacing a single Na(+) ion along the pore of the CRAC channel. The computed PMF indicates that the central hydrophobic region provides the major hindrance for ion diffusion along the permeation pathway, thereby illustrating the nonconducting nature of the crystal structure conformation. Strikingly, further PMF calculations demonstrate that the mutation V174A decreases the free energy barrier for conduction, rendering the channel effectively open. This seemingly dramatic effect of mutating a nonpolar residue for a smaller nonpolar residue in the pore hydrophobic region suggests an important role for the latter in conduction. Indeed, our computations show that even without significant channel-gating motions, a subtle change in the number of pore waters is sufficient to reshape the local electrostatic field and modulate the energetics of conduction, a result that rationalizes recent experimental findings. The present work suggests the activation mechanism for the wild-type CRAC channel is likely regulated by the number of pore waters and hence pore hydration governs the conductance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.