AMPK β subunits display isoform specific affinities for carbohydrates

AMP-activated protein kinase (AMPK) is a heterotrimer of catalytic (alpha) and regulatory (beta and gamma) subunits with at least two isoforms for each subunit. AMPK w beta 1 is widely expressed whilst AMPK beta 2 is highly expressed in muscle and both beta isoforms contain a mid-molecule carbohydrate-binding module (beta-CBM). Here we show that beta 2-CBM has evolved to contain a Thr insertion and increased affinity for glycogen mimetics with a preference for oligosaccharides containing a single alpha-1,6 branched residue. Deletion of Thr-101 reduces affinity for single alpha-1,6 branched oligosaccharides by 3-fold, while insertion of this residue into the equivalent position in the beta 1-CBM sequence increases affinity by 3-fold, confirming the functional importance of this residue. (C) 2010 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.