A region of the sulfonylurea receptor critical for a modulation of ATP-sensitive K+ channels by G-protein [beta][gamma]-subunits

To determine the interaction site(s) of ATP-sensitive K+ (KATP) channels for G-proteins, sulfonylurea receptor (SUR2A or SUR1) and pore-forming (Kir6.2) subunits were reconstituted in the mammalian cell line, COS-7. Intracellular application of the G-protein [beta][gamma]2-subunits (G[beta][gamma]2)...

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Bibliographic Details
Published in:The EMBO journal 2000-09, Vol.19 (18), p.4915
Main Authors: Wada, Yoshiyuki, Yamashita, Toshikazu, Imai, Kohbun, Miura, Reiko, Takao, Kyoichi, Nishi, Miyuki, Takeshima, Hiroshi, Asano, Tomiko, Morishita, Rika, Nishizawa, Kazuhisa, Kokubun, Shinichiro, Nukada, Toshihide
Format: Article
Language:English
Subjects:
Amino acids
ATP
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Summary:To determine the interaction site(s) of ATP-sensitive K+ (KATP) channels for G-proteins, sulfonylurea receptor (SUR2A or SUR1) and pore-forming (Kir6.2) subunits were reconstituted in the mammalian cell line, COS-7. Intracellular application of the G-protein [beta][gamma]2-subunits (G[beta][gamma]2) caused a reduction of ATP-induced inhibition of Kir6.2/SUR channel activities by lessening the ATP sensitivity of the channels. G[beta][gamma]2 bound in vitroto both intracellular (loop-NBD) and C-terminal segments of SUR2A, each containing a nucleotide-binding domain (NBD). Furthermore, a single amino acid substitution in the loop-NBD of SUR (Arg656Ala in SUR2A or Arg665Ala in SUR1) abolished the G[beta][gamma]2-dependent alteration of the channel activities. These findings provide evidence that G[beta][gamma] modulates KATP channels through a direct interaction with the loop-NBD of SUR.
ISSN:0261-4189
1460-2075