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Circulation Research. 2002
Published online before print February 7, 2002, doi: 10.1161/01.RES.0000012666.42782.30
A more recent version of this article appeared on March 22, 2002
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Submitted on October 23, 2001
Revised on January 29, 2002
Accepted on January 30, 2002

Intramolecular Interaction of SUR2 Subtypes for Intracellular ADP-Induced Differential Control of KATP Channels

Kenji Matsushita ; Kengo Kinoshita ; Tetsuro Matsuoka ; Akikazu Fujita ; Takashi Fujikado ; Yasuo Tano ; Haruki Nakamura ; and Yoshihisa Kurachi *

From the Departments of Pharmacology II (K.M., T.M., A.F., Y.K.) and Ophthalmology (K.M., T.F., Y.T.), Graduate School of Medicine, and the Research Center For Structural Biology (H.N.), Institute for Protein Research, Osaka University, Suita, Osaka, Japan; and the Division of Science of Biological Supramolecular Systems (K.K.), Graduate School of Integrated Science, Yokohama University, Yokohama, Kanagawa, Japan.

* To whom correspondence should be addressed. E-mail: ykurachi{at}pharma2.med.osaka-u.ac.jp.

ATP-sensitive K+ (KATP) 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 KATP channels in SUR-subtypes. By examining ADP-effect on KATP 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 KATP channels.


Key words: homology modeling • KATP channel • nucleotide binding domain • sulfonylurea receptor • Walker motif




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