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Journal of Experimental Biology, Vol 203, Issue 13 1947-1962, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
NA McCarty
Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322-3110, USA. NMCC@physio.emory.edu
The cystic fibrosis transmembrane conductance regulator (CFTR) protein forms a Cl(-) channel found in the plasma membranes of many epithelial cells, including those of the kidney, gut and conducting airways. Mutation of the gene encoding CFTR is the primary defect in cystic fibrosis, a disease that affects approximately 30 000 individuals in the United States alone. Alteration of CFTR function also plays an important role in the pathophysiology of secretory diarrhea and polycystic kidney disease. The basic mechanisms of permeation in this channel are not well understood. It is not known which portions of the protein contribute to forming the pore or which amino acid residues in those domains are involved in the biophysical processes of ion permeation. In this review, I will discuss (i) the present understanding of ion transport processes in the wild-type CFTR channel, (ii) the experimental approaches currently being applied to investigate the pore, and (iii) a proposed structure that takes into account the present data on mechanisms of ion selectivity in the CFTR channel and on blockade of the pore by open-channel blockers.
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Z.-R. Zhang, B. Song, and N. A. McCarty State-dependent Chemical Reactivity of an Engineered Cysteine Reveals Conformational Changes in the Outer Vestibule of the Cystic Fibrosis Transmembrane Conductance Regulator J. Biol. Chem., December 23, 2005; 280(51): 41997 - 42003. [Abstract] [Full Text] [PDF]
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M. D. Fuller, Z.-R. Zhang, G. Cui, and N. A. McCarty The Block of CFTR by Scorpion Venom is State-Dependent Biophys. J., December 1, 2005; 89(6): 3960 - 3975. [Abstract] [Full Text] [PDF]
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Z.-R. Zhang, G. Cui, X. Liu, B. Song, D. C. Dawson, and N. A. McCarty Determination of the Functional Unit of the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel: ONE POLYPEPTIDE FORMS ONE PORE J. Biol. Chem., January 7, 2005; 280(1): 458 - 468. [Abstract] [Full Text] [PDF]
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 Z.-R. Zhang, S. Zeltwanger, S. S. Smith, D. C. Dawson, and N. A. McCarty Voltage-sensitive gating induced by a mutation in the fifth transmembrane domain of CFTR Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L135 - L145. [Abstract] [Full Text] [PDF]
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N. A. McCarty and Z.-R. Zhang Identification of a region of strong discrimination in the pore of CFTR Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L852 - L867. [Abstract] [Full Text] [PDF]
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J. Fu and K. L. Kirk Cysteine Substitutions Reveal Dual Functions of the Amino-terminal Tail in Cystic Fibrosis Transmembrane Conductance Regulator Channel Gating J. Biol. Chem., September 14, 2001; 276(38): 35660 - 35668. [Abstract] [Full Text] [PDF]
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