Journal
FEBS LETTERS
Volume 499, Issue 1-2, Pages 154-160Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(01)02538-8
Keywords
potassium channel; sulfonylurea receptor; baculovirus; ATP binding cassette protein; SUR1/ABCC8
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We have investigated the structure of the glibenclamide binding site of pancreatic beta -cell ATP-sensitive potassium (K-ATP) channels. KATP channels are a complex of four poreforming Kir6.2 subunits and four sulfonylurea receptor (SUR1) subunits, SUR1 (ABCC8) belongs to the;LTP binding cassette family of proteins and has two nucleotide binding domains (NBD1 and NBD2) and 17 putative transmembrane (TRI) sequences. Co-expression in a baculovirus expression system of two parts of SUR1 between NBD1 and TM12 leads to restoration of glibenclamide binding activity, whereas expression of either individual N- or C-terminal part alone gave no glibenclamide binding activity, confirming a bivalent structure of the glibenclamide binding site, By using N-terminally truncated recombinant proteins we hare shown that CL3 - the cytosolic loop between TM5 and TM6 - plays a key role in formation of the IV-terminal component of the glibenclamide binding site. Analysis of deletion variants of the C-terminal part of SUR1 showed that CL8 - the cytosolic loop between TM15 and TM16 - is the only determinant for the C-terminal component of the glibenclamide binding site. We suggest that in SUR1 in the native KATP channel close proximity of CU and CL8 leads to formation of the glibenclamide binding site. (C) 2001 Published by Elsevier Science B,V. on behalf of the Federation of European Biochemical Societies.
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