ArticleBiochemistry2012
Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path and locates a "bottleneck" in the pore.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Stability Prediction for Mutations in the Cytosolic Domains of Cystic Fibrosis Transmembrane Conductance Regulator.Journal of chemical information and modeling · 2021Article
- Discovering the chloride pathway in the CFTR channel.Cellular and molecular life sciences : CMLS · 2020Article
- Contribution of the eighth transmembrane segment to the function of the CFTR chloride channel pore.Cellular and molecular life sciences : CMLS · 2019Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
- Functional characterization reveals that zebrafish CFTR prefers to occupy closed channel conformations.PloS one · 2018Article
- Transmembrane helical interactions in the CFTR channel pore.PLoS computational biology · 2017Article
- The biophysics, biochemistry and physiology of CFTR.Cellular and molecular life sciences : CMLS · 2017Review
- Cytoplasmic pathway followed by chloride ions to enter the CFTR channel pore.Cellular and molecular life sciences : CMLS · 2016Article
- Spatial positioning of CFTR's pore-lining residues affirms an asymmetrical contribution of transmembrane segments to the anion permeation pathway.The Journal of general physiology · 2016Article
- Long-range coupling between the extracellular gates and the intracellular ATP binding domains of multidrug resistance protein pumps and cystic fibrosis transmembrane conductance regulator channels.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Cystic Fibrosis Transmembrane Conductance Regulator (CFTR): CLOSED AND OPEN STATE CHANNEL MODELS.The Journal of biological chemistry · 2015Article
- The Fifth Transmembrane Segment of Cystic Fibrosis Transmembrane Conductance Regulator Contributes to Its Anion Permeation Pathway.Biochemistry · 2015Article
- Impact of the F508del mutation on ovine CFTR, a Cl- channel with enhanced conductance and ATP-dependent gating.The Journal of physiology · 2015Article
- Full-open and closed CFTR channels, with lateral tunnels from the cytoplasm and an alternative position of the F508 region, as revealed by molecular dynamics.Cellular and molecular life sciences : CMLS · 2015Article
- Localizing a gate in CFTR.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- An electrostatic interaction at the tetrahelix bundle promotes phosphorylation-dependent cystic fibrosis transmembrane conductance regulator (CFTR) channel opening.The Journal of biological chemistry · 2014Article
- Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.The Journal of biological chemistry · 2014Article
- Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.PLoS genetics · 2014Article
- Relative contribution of different transmembrane segments to the CFTR chloride channel pore.Pflugers Archiv : European journal of physiology · 2014Article
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Authors and funding
7 authors.
Funding
Abstract
We developed molecular models for the cystic fibrosis transmembrane conductance regulator chloride channel based on the prokaryotic ABC transporter, Sav1866. Here we analyze predicted pore geometry and side-chain orientations for TM3, TM6, TM9, and TM12, with particular attention being paid to the location of the rate-limiting barrier for anion conduction. Side-chain orientations assayed by cysteine scanning were found to be from 77 to 90% in accord with model predictions. The predicted geometry of the anion conduction path was defined by a space-filling model of the pore and confirmed by visualizing the distribution of water molecules from a molecular dynamics simulation. The pore shape is that of an asymmetric hourglass, comprising a shallow outward-facing vestibule that tapers rapidly toward a narrow "bottleneck" linking the outer vestibule to a large inner cavity extending toward the cytoplasmic extent of the lipid bilayer. The junction between the outer vestibule and the bottleneck features an outward-facing rim marked by T338 in TM6 and I1131 in TM12, consistent with the observation that cysteines at both of these locations reacted with both channel-permeant and channel-impermeant, thiol-directed reagents. Conversely, cysteines substituted for S341 in TM6 or T1134 in TM12, predicted by the model to lie below the rim of the bottleneck, were found to react exclusively with channel-permeant reagents applied from the extracellular side. The predicted dimensions of the bottleneck are consistent with the demonstrated permeation of Cl(-), pseudohalide anions, water, and urea.
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