AMP-activated protein kinase β subunit tethers α and γ subunits via its c-terminal sequence (186-270)

Abstract

AMP-activated protein kinase (AMPK) is an important metabolic stress-sensing protein kinase responsible for regulating metabolism in response to changing energy demand and nutrient supply. Mammalian AMPK is a stable αβγ heterotrimer comprising a catalytic α and two non-catalytic subunits, β and γ. The β subunit targets AMPK to membranes via an N-terminal myristoyl group and to glycogen via a mid-molecule glycogen-binding domain. Here we find that the conserved C-terminal 85-residue sequence of the β subunit, β1-(186-270), is sufficient to form an active AMP-dependent heterotrimer α1β1-(186-270)-γ1, whereas the 25-residue β1 C-terminal (246-270) sequence is sufficient to bind γ1, γ2, or γ3 bu..