AMPK α1β2γ1

AMPK α1β2γ1 is an AMP-activated protein kinase heterotrimer composed of catalytic α and regulatory β/γ subunits, linking cellular energy sensing with energy homeostasis^[1]. Mechanistically, AMP and glycogen regulate human α1β2γ1 holo-AMPK through nucleotide-dependent and glycogen-mimic interactions, supporting its use in structural studies of allosteric regulation^[1]. In human liver, chemoproteomic profiling identified α1β2γ1 as the predominant AMPK heterotrimer, whereas dog and rat livers mainly contained α1β1γ1 and α2β1γ1 forms^[2]. In human skeletal muscle, only three AMPK trimer combinations were detected, and α1β2γ1 appeared with α2β2γ1 and α2β2γ3, providing a disease-relevant context for type 2 diabetes and training studies^[3]. Compared with α2 complexes, α1-containing AMPK complexes showed higher specific activity and lower K_m for SAMS peptide, while β2-containing isoforms were less sensitive to A769662 than β1 isoforms^[4]. For agonist design, C2 activated α1β1γ1 and α1β2γ1 γ1 complexes, whereas SC4 showed poor activation potential against α1β2γ1^[5][6].