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  • The EMBO Journal (2005) 24, 1318 - 1329
  • doi:10.1038/sj.emboj.7600626

Published online: 17 March 2005

Novel nucleotide-binding sites in ATP-sensitive potassium channels formed at gating interfaces

Ke Dong1, Lie-Qi Tang1, Gordon G MacGregor1, Qiang Leng1 and Steven C Hebert1

  1. Department of Cellular and Molecular Physiology, School of Medicine, Yale University, New Haven, CT, USA

Correspondence to:

Steven C Hebert, Department of Cellular and Molecular Physiology, School of Medicine, Yale University, 333 Cedar Street, New Haven, CT 06520, USA. Tel.: +1 203 785 4041; Fax: +1 203 785 7678; E-mail: steven.hebert@yale.edu

Received 14 September 2004; Accepted 15 February 2005

The coupling of cell metabolism to membrane electrical activity is a vital process that regulates insulin secretion, cardiac and neuronal excitability and the responses of cells to ischemia. ATP-sensitive potassium channels (KATP; Kir6.x) are a major part of this metabolic–electrical coupling system and translate metabolic signals such as the ATP:ADP ratio to changes in the open or closed state (gate) of the channel. The localization of the nucleotide-binding site (NBS) on Kir6.x channels and how nucleotide binding gates these KATP channels remain unclear. Here, we use fluorescent nucleotide binding to purified Kir6.x proteins to define the peptide segments forming the NBS on Kir6.x channels and show that unique N- and C-terminal interactions from adjacent subunits are required for high-affinity nucleotide binding. The short N- and C-terminal segments comprising the novel intermolecular NBS are next to helices that likely move with channel opening/closing, suggesting a lock-and-key model for ligand gating.

  • Keywords:

    • ATP-sensitive potassium channel,
    • inward rectifier potassium channel,
    • nucleotide-binding site,
    • 8-azido-[gamma-32P]ATP,
    • TNP-ATP