Journal article
Structural and functional similarities between the nucleotide-binding domains of CFTR and GTP-binding proteins
Biophysical journal, Vol.69(6), pp.2443-2448
12/1995
DOI: 10.1016/S0006-3495(95)80113-X
PMID: 8599650
Abstract
The opening and closing of the CFTR Cl- channel are regulated by ATP hydrolysis at its two nucleotide binding domains (NBDs). However, the mechanism and functional significance of ATP hydrolysis are unknown. Sequence similarity between the NBDs of CFTR and GTP-binding proteins suggested the NBDs might have a structure and perhaps a function like that of GTP-binding proteins. Based on this similarity, we predicted that the terminal residue of the LSGGQ motif in the NBDs of CFTR corresponds to a highly conserved glutamine residue in GTP-binding proteins that directly catalyzes the GTPase reaction. Mutations of this residue in NBD1 or NBD2, which were predicted to increase or decrease the rate of hydrolysis, altered the duration of channel closed and open times in a specific manner without altering ion conduction properties or ADP-dependent inhibition. These results suggest that the NBDs of CFTR, and consequently other ABC transporters, may have a structure and a function analogous to those of GTP-binding proteins. We conclude that the rates of ATP hydrolysis at NBD1 and at NBD2 determine the duration of the two states of the channel, closed and open, much as the rate of GTP hydrolysis by GTP-binding proteins determines the duration of their active state.
Details
- Title: Subtitle
- Structural and functional similarities between the nucleotide-binding domains of CFTR and GTP-binding proteins
- Creators
- Mark R Carson - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USAMichael J Welsh - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA
- Resource Type
- Journal article
- Publication Details
- Biophysical journal, Vol.69(6), pp.2443-2448
- DOI
- 10.1016/S0006-3495(95)80113-X
- PMID
- 8599650
- ISSN
- 0006-3495
- eISSN
- 1542-0086
- Language
- English
- Date published
- 12/1995
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Neurosurgery; Internal Medicine
- Record Identifier
- 9984018825102771
Metrics
19 Record Views