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Novel nucleotide‐binding sites in ATP‐sensitive potassium channels formed at gating interfaces
Author(s) -
Dong Ke,
Tang LieQi,
MacGregor Gordon G,
Leng Qiang,
Hebert Steven C
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600626
Subject(s) - biology , nucleotide , potassium channel , gating , biophysics , binding site , adenosine triphosphate , biochemistry , microbiology and biotechnology , genetics , gene
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 (K ATP ; 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 K ATP 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.