Journal article
Tandem Function of Nucleotide Binding Domains Confers Competence to Sulfonylurea Receptor in Gating ATP-sensitive K+ Channels
The Journal of biological chemistry, Vol.277(16), pp.14206-14210
04/19/2002
DOI: 10.1074/jbc.M109452200
PMID: 11825892
Abstract
Fundamental to the metabolic sensor function of ATP-sensitive K+ (KATP) channels is the sulfonylurea receptor. This ATP-binding cassette protein, which contains nucleotide binding domains (NBD1 and NBD2) with conserved Walker motifs, regulates the ATP sensitivity of the pore-forming Kir6.2 subunit. Although NBD2 hydrolyzes ATP, a property essential in KATP channel gating, the role of NBD1, which has limited catalytic activity, if at all, remains less understood. Here, we provide functional evidence that cooperative interaction, rather than the independent contribution of each NBD, is critical for KATP channel regulation. Gating of cardiac KATPchannels by distinct conformations in the NBD2 ATPase cycle, induced by γ-phosphate analogs, was disrupted by point mutation not only of the Walker motif in NBD2 but also in NBD1. Cooling membrane patches to decelerate the intrinsic ATPase activity counteracted ATP-induced KATP channel inhibition, an effect that mimicked stabilization of the MgADP-bound posthydrolytic state at NBD2 by the γ-phosphate analog orthovanadate. Temperature-induced channel activation was abolished by mutations that either prevent stabilization of MgADP at NBD2 or ATP at NBD1. These findings provide a paradigm of KATP channel gating based on integration of both NBDs into a functional unit within the multimeric channel complex.
Details
- Title: Subtitle
- Tandem Function of Nucleotide Binding Domains Confers Competence to Sulfonylurea Receptor in Gating ATP-sensitive K+ Channels
- Creators
- Leonid V Zingman - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905Denice M Hodgson - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905Martin Bienengraeber - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905Amy B Karger - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905Eva C Kathmann - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905Alexey E Alekseev - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905Andre Terzic - Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.277(16), pp.14206-14210
- DOI
- 10.1074/jbc.M109452200
- PMID
- 11825892
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/19/2002
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094402302771
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