Intramolecular interaction of SUR2 subtypes for intracellular ADP-Induced differential control of K(ATP) channels.
ATP-sensitive K+ (K(ATP)) channels are composed of sulfonylurea receptors (SURs) and inwardly rectifying Kir6.2-channels. The C-terminal 42 amino acid residues (C42) of SURs are responsible for ADP-induced differential activation of K(ATP) channels in SUR-subtypes. By examining ADP-effect on K(ATP) channels containing various chimeras of SUR2A and SUR2B, we identified a segment of 7 residues at central portion of C42 critical for this phenomenon. A 3-D structure model of the region containing the second nucleotide-binding domain (NBD2) of SUR and C42 was developed based on the structure of HisP, a nucleotide-binding protein forming the bacterial Histidine transporter complex. In the model, the polar and charged residues in the critical segment located within a distance that allows their electrostatic interaction with Arg1344 at the Walker-A loop of NBD2. Therefore, the interaction might be involved in the control of ADP-induced differential activation of SUR2-subtype K(ATP) channels.
Matsushita
Kenji
K
Department of Pharmacology II, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Kinoshita
Kengo
K
Matsuoka
Tetsuro
T
Fujita
Akikazu
A
Fujikado
Takashi
T
Tano
Yasuo
Y
Nakamura
Haruki
H
Kurachi
Yoshihisa
Y
D018528:ATP-Binding Cassette Transporters; D000244:Adenosine Diphosphate / Q000378:metabolism* / Q000494:pharmacology; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D064233:Sulfonylurea Receptors; D014162:Transfection
C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; C577511:Abcc9 protein, mouse; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D011993:Recombinant Fusion Proteins; D064233:Sulfonylurea Receptors; D000244:Adenosine Diphosphate