ArticleThe Journal of membrane biology2007
Direct and indirect effects of mutations at the outer mouth of the cystic fibrosis transmembrane conductance regulator chloride channel pore.
Article in The Journal of membrane biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Role of Hydrophobic Amino-Acid Side-Chains in the Narrow Selectivity Filter of the CFTR Chloride Channel Pore in Conductance and Selectivity.The Journal of membrane biology · 2023Article
- Functional organization of cytoplasmic portals controlling access to the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel pore.The Journal of biological chemistry · 2018Article
- Architecture and functional properties of the CFTR channel pore.Cellular and molecular life sciences : CMLS · 2017Review
- The Fifth Transmembrane Segment of Cystic Fibrosis Transmembrane Conductance Regulator Contributes to Its Anion Permeation Pathway.Biochemistry · 2015Article
- Location of a permeant anion binding site in the cystic fibrosis transmembrane conductance regulator chloride channel pore.The journal of physiological sciences : JPS · 2015Article
- State-dependent blocker interactions with the CFTR chloride channel: implications for gating the pore.Pflugers Archiv : European journal of physiology · 2014Article
- Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance.World journal of biological chemistry · 2014Review
- Locating a plausible binding site for an open-channel blocker, GlyH-101, in the pore of the cystic fibrosis transmembrane conductance regulator.Molecular pharmacology · 2012Article
- Pseudohalide anions reveal a novel extracellular site for potentiators to increase CFTR function.British journal of pharmacology · 2012Article
- Relative movements of transmembrane regions at the outer mouth of the cystic fibrosis transmembrane conductance regulator channel pore during channel gating.The Journal of biological chemistry · 2012Article
- Differential contribution of TM6 and TM12 to the pore of CFTR identified by three sulfonylurea-based blockers.Pflugers Archiv : European journal of physiology · 2012Article
- ATP hydrolysis-dependent asymmetry of the conformation of CFTR channel pore.The journal of physiological sciences : JPS · 2011Article
- Regulation of conductance by the number of fixed positive charges in the intracellular vestibule of the CFTR chloride channel pore.The Journal of general physiology · 2010Article
- Cysteine-independent inhibition of the CFTR chloride channel by the cysteine-reactive reagent sodium (2-sulphonatoethyl) methanethiosulphonate.British journal of pharmacology · 2009Article
- Novel residues lining the CFTR chloride channel pore identified by functional modification of introduced cysteines.The Journal of membrane biology · 2009Article
- Identification of positive charges situated at the outer mouth of the CFTR chloride channel pore.Pflugers Archiv : European journal of physiology · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel pore is thought to contain multiple binding sites for permeant and impermeant anions. Here, we investigate the effects of mutation of different positively charged residues in the pore on current inhibition by impermeant Pt(NO(2)) (4) (2-) and suramin anions. We show that mutations that remove positive charges (K95, R303) influence interactions with intracellular, but not extracellular, Pt(NO(2))(4)(2-) ions, consistent with these residues being situated within the pore inner vestibule. In contrast, mutation of R334, supposedly located in the outer vestibule of the pore, affects block by both extracellular and intracellular Pt(NO(2))(4)(2-). Inhibition by extracellular Pt(NO(2))(4)(2-) requires a positive charge at position 334, consistent with a direct electrostatic interaction resulting in either open channel block or surface charge screening. In contrast, inhibition by intracellular Pt(NO(2))(4)(2-) is weakened in all R334-mutant forms of the channel studied, inconsistent with a direct interaction. Furthermore, mutation of R334 had similar effects on block by intracellular suramin, a large organic molecule that is apparently unable to enter deeply into the channel pore. Mutation of R334 altered interactions between intracellular Pt(NO(2))(4)(2-) and extracellular Cl(-) but not those between intracellular Pt(NO(2))(4)(2-) and extracellular Pt(NO(2))(4)(2-). We propose that while the positive charge of R334 interacts directly with extracellular anions, mutation of this residue also alters interactions with intracellular anions by an indirect mechanism, due to mutation-induced conformational changes in the protein that are propagated some distance from the site of the mutation in the outer mouth of the pore.
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