Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biophys J
2004 Dec 01;876:3826-41. doi: 10.1529/biophysj.104.050534.
Show Gene links
Show Anatomy links
CFTR: a cysteine at position 338 in TM6 senses a positive electrostatic potential in the pore.
Liu X
,
Zhang ZR
,
Fuller MD
,
Billingsley J
,
McCarty NA
,
Dawson DC
.
???displayArticle.abstract???
We investigated the accessibility to protons and thiol-directed reagents of a cysteine substituted at position 338 in transmembrane segment 6 (TM6) of CFTR to test the hypothesis that T338 resides in the pore. Xenopus oocytes expressing T338C CFTR exhibited pH-dependent changes in gCl and I-V shape that were specific to the substituted cysteine. The apparent pKa of T338C CFTR was more acidic than that expected for a cysteine or similar simple thiols in aqueous solution. The pKa was shifted toward alkaline values when a nearby positive charge (R334) was substituted with neutral or negatively charged residues, consistent with the predicted influence of the positive charge of R334, and perhaps other residues, on the titration of a cysteine at 338. The relative rates of chemical modification of T338C CFTR by MTSET+ and MTSES- were also altered by the charge at 334. These observations support a model for CFTR that places T338 within the anion conduction path. The apparent pKa of a cysteine substituted at 338 and the relative rates of reaction of charged thiol-directed reagents provide a crude measure of a positive electrostatic potential that may be due to R334 and other residues near this position in the pore.
Akabas,
Channel-lining residues in the M3 membrane-spanning segment of the cystic fibrosis transmembrane conductance regulator.
1998, Pubmed,
Xenbase
Akabas,
Channel-lining residues in the M3 membrane-spanning segment of the cystic fibrosis transmembrane conductance regulator.
1998,
Pubmed
,
Xenbase
Antosiewicz,
Prediction of pH-dependent properties of proteins.
1994,
Pubmed
Antosiewicz,
The determinants of pKas in proteins.
1996,
Pubmed
Bashford,
Electrostatic calculations of the pKa values of ionizable groups in bacteriorhodopsin.
1992,
Pubmed
Bashford,
pKa's of ionizable groups in proteins: atomic detail from a continuum electrostatic model.
1990,
Pubmed
Begenisich,
Sodium channel permeation in squid axons. II: Non-independence and current-voltage relations.
1980,
Pubmed
Cai,
How does vestibule surface charge affect ion conduction and toxin binding in a sodium channel?
1990,
Pubmed
Cheung,
Locating the anion-selectivity filter of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel.
1997,
Pubmed
Cheung,
Identification of cystic fibrosis transmembrane conductance regulator channel-lining residues in and flanking the M6 membrane-spanning segment.
1996,
Pubmed
,
Xenbase
Cotten,
Cystic fibrosis-associated mutations at arginine 347 alter the pore architecture of CFTR. Evidence for disruption of a salt bridge.
1999,
Pubmed
Dani,
Ion-channel entrances influence permeation. Net charge, size, shape, and binding considerations.
1986,
Pubmed
Dillet,
Calculations of electrostatic interactions and pKas in the active site of Escherichia coli thioredoxin.
1998,
Pubmed
Elinder,
S4 charges move close to residues in the pore domain during activation in a K channel.
2001,
Pubmed
,
Xenbase
Fitch,
Experimental pK(a) values of buried residues: analysis with continuum methods and role of water penetration.
2002,
Pubmed
Giles,
Multiple roles of cysteine in biocatalysis.
2003,
Pubmed
Gilson,
Energetics of charge-charge interactions in proteins.
1988,
Pubmed
Goldman,
POTENTIAL, IMPEDANCE, AND RECTIFICATION IN MEMBRANES.
1943,
Pubmed
Harrington,
Redox reagents and divalent cations alter the kinetics of cystic fibrosis transmembrane conductance regulator channel gating.
1999,
Pubmed
Jacob,
Sulfur and selenium: the role of oxidation state in protein structure and function.
2003,
Pubmed
Karlin,
Substituted-cysteine accessibility method.
1998,
Pubmed
Kortemme,
Ionisation of cysteine residues at the termini of model alpha-helical peptides. Relevance to unusual thiol pKa values in proteins of the thioredoxin family.
1995,
Pubmed
LINDLEY,
A study of the kinetics of the reaction between thiol compounds and choloracetamide.
1960,
Pubmed
Linsdell,
Permeability of wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride channels to polyatomic anions.
1997,
Pubmed
Linsdell,
Non-pore lining amino acid side chains influence anion selectivity of the human CFTR Cl- channel expressed in mammalian cell lines.
1998,
Pubmed
Linsdell,
Molecular determinants of anion selectivity in the cystic fibrosis transmembrane conductance regulator chloride channel pore.
2000,
Pubmed
Liu,
CFTR: covalent modification of cysteine-substituted channels expressed in Xenopus oocytes shows that activation is due to the opening of channels resident in the plasma membrane.
2001,
Pubmed
,
Xenbase
Lu,
Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel.
1994,
Pubmed
,
Xenbase
MacKinnon,
Role of surface electrostatics in the operation of a high-conductance Ca2+-activated K+ channel.
1989,
Pubmed
Mansoura,
Cystic fibrosis transmembrane conductance regulator (CFTR) anion binding as a probe of the pore.
1998,
Pubmed
,
Xenbase
McCarty,
Identification of a region of strong discrimination in the pore of CFTR.
2001,
Pubmed
,
Xenbase
McLaughlin,
The electrostatic properties of membranes.
1989,
Pubmed
Mehler,
Comparison of dielectric response models for simulating electrostatic effects in proteins.
1990,
Pubmed
Mehler,
A self-consistent, microenvironment modulated screened coulomb potential approximation to calculate pH-dependent electrostatic effects in proteins.
1999,
Pubmed
Oberoi,
Multigrid solution of the nonlinear Poisson-Boltzmann equation and calculation of titration curves.
1993,
Pubmed
Pascual,
Delimiting the binding site for quaternary ammonium lidocaine derivatives in the acetylcholine receptor channel.
1998,
Pubmed
,
Xenbase
Peters,
Electrostatic evaluation of the signature motif (H/V)CX5R(S/T) in protein-tyrosine phosphatases.
1998,
Pubmed
Pickersgill,
A rapid method of calculating charge-charge interaction energies in proteins.
1988,
Pubmed
Roberts,
Reactivity of small thiolate anions and cysteine-25 in papain toward methyl methanethiosulfonate.
1986,
Pubmed
Rojas,
Acetylcholine receptor channel gating and conductance involve extracellular disulfide bond(s).
1991,
Pubmed
,
Xenbase
Schutz,
What are the dielectric "constants" of proteins and how to validate electrostatic models?
2001,
Pubmed
Sham,
The effect of protein relaxation on charge-charge interactions and dielectric constants of proteins.
1998,
Pubmed
Sheppard,
Mutations in CFTR associated with mild-disease-form Cl- channels with altered pore properties.
1993,
Pubmed
Smit,
Functional roles of the nucleotide-binding folds in the activation of the cystic fibrosis transmembrane conductance regulator.
1993,
Pubmed
,
Xenbase
Smith,
CFTR: covalent and noncovalent modification suggests a role for fixed charges in anion conduction.
2001,
Pubmed
,
Xenbase
Smith,
Cystic fibrosis transmembrane conductance regulator. Physical basis for lyotropic anion selectivity patterns.
1999,
Pubmed
,
Xenbase
Stauffer,
Electrostatic potential of the acetylcholine binding sites in the nicotinic receptor probed by reactions of binding-site cysteines with charged methanethiosulfonates.
1994,
Pubmed
Wilkinson,
CFTR: the nucleotide binding folds regulate the accessibility and stability of the activated state.
1996,
Pubmed
,
Xenbase
Wilson,
The intrinsic electrostatic potential and the intermediate ring of charge in the acetylcholine receptor channel.
2000,
Pubmed
,
Xenbase
Yang,
On the calculation of pKas in proteins.
1993,
Pubmed
Zhang,
Interaction between permeation and gating in a putative pore domain mutant in the cystic fibrosis transmembrane conductance regulator.
2000,
Pubmed
,
Xenbase
Zhang,
Voltage-sensitive gating induced by a mutation in the fifth transmembrane domain of CFTR.
2002,
Pubmed
,
Xenbase
