Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide

Citation
K. Ueda et al., Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide, P NAS US, 96(4), 1999, pp. 1268-1272
Citations number
33
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
96
Issue
4
Year of publication
1999
Pages
1268 - 1272
Database
ISI
SICI code
0027-8424(19990216)96:4<1268:CBOAAM>2.0.ZU;2-8
Abstract
The ATP-sensitive potassium (K-ATP) channels in pancreatic beta cells are c ritical in the regulation of glucose-induced insulin secretion. Although el ectrophysiological studies provide clues to the complex control of K-ATP ch annels by ATP, MgADP, and pharmacological agents, the molecular mechanism o f K-ATP-channel regulation remains unclear. The K-ATP channel is a heterool igomeric complex of SUR1 subunits of the ATP-binding-cassette superfamily w ith two nucleotide-binding folds (NBF1 and NBF2) and the pore-forming Kir6. 2 subunits. Here, we report that MgATP and MgADP, but not the Mg salt of ga mma-thio-ATP, stabilize the binding of prebound 8-azido-[alpha-P-32]ATP to SUR1. Mutation in the Walker A and B motifs of NBF2 of SUR1. abolished this stabilizing effect of MgADP. These results suggest that SUR1 binds 8-azido -ATP strongly at NBF1 and that MgADP, either by direct binding to NBF2 or b y hydrolysis of bound MgATP at NBF2, stabilizes prebound 8-azido-ATP bindin g at NBF1. The sulfonylurea glibenclamide caused release of prebound 8-azid o-[alpha-P-32]ATP from SUR1 in the presence of MgADP or MgATP in a concentr ation-dependent manner. This direct biochemical evidence of cooperative int eraction in nucleotide binding of the two NBFs of SUR1 suggests that gliben clamide both blocks this cooperative binding of ATP and MgADP and, in coope ration with the MgADP bound at NBF2, causes ATP to be released from NBF1.