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A region of the sulfonylurea receptor critical for a modulation of ATP‐sensitive K + channels by G‐protein βγ‐subunits
Author(s) -
Wada Yoshiyuki,
Yamashita Toshikazu,
Imai Kohbun,
Miura Reiko,
Takao Kyoichi,
Nishi Miyuki,
Takeshima Hiroshi,
Asano Tomiko,
Morishita Rika,
Nishizawa Kazuhisa,
Kokubun Shinichiro,
Nukada Toshihide
Publication year - 2000
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 - 10.1093/emboj/19.18.4915
Subject(s) - biology , sulfonylurea receptor , sulfonylurea , g protein , protein subunit , microbiology and biotechnology , receptor , biophysics , biochemistry , endocrinology , gene , insulin
To determine the interaction site(s) of ATP‐sensitive K + (K ATP ) 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 βγ2‐subunits (G βγ2 ) caused a reduction of ATP‐induced inhibition of Kir6.2/SUR channel activities by lessening the ATP sensitivity of the channels. G βγ2 bound in vitro to 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 βγ2 ‐dependent alteration of the channel activities. These findings provide evidence that G βγ modulates K ATP channels through a direct interaction with the loop‐NBD of SUR.