AMPK beta 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 beta1 is widely expressed whilst AMPK beta2 is highly expressed in muscle and both beta isoforms contain a mid-molecule carbohydrate-binding module (beta-CBM). Here we show that beta2-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 beta1-CBM sequence increases affinity by 3-fold, confirming the functional importance of this residue.
Koay
Ann
A
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
Woodcroft
Ben
B
Petrie
Emma J
EJ
Yue
Helen
H
Emanuelle
Shane
S
Bieri
Michael
M
Bailey
Michael F
MF
Hargreaves
Mark
M
Park
Jong-Tae
JT
Park
Kwan-Hwa
KH
Ralph
Stuart
S
Neumann
Dietbert
D
Stapleton
David
D
Gooley
Paul R
PR
D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002417:Cattle; D019295:Computational Biology; D006003:Glycogen / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D007527:Isoenzymes; D009844:Oligosaccharides; D021122:Protein Subunits; D006003:Glycogen; D055372:AMP-Activated Protein Kinases