![]() Data pooled from three biological replicates. Representative plot of three biological replicates shown. Data shown is normalised to untreated WT/N2 phosphorylation. Graph shows quantification from three biological replicates, representative blot shown below the graph. Western blot analysis with and without 4.5mM phenformin. Phosphorylation of the AAK-2 protein (α subunit) at Thr172. Mutant alleles of each γ isoform were combined genetically to create strains that we predict act AMP-dependently or AMP-independently. Has five AMPKγ isoforms which can be grouped by the presence or absence of conserved residues predicted to influence its ability to bind AMP (as in A multiple sequence alignment is shown below: deeper colouring indicates higher conservation between sequences, and key predicted AMP binding residues are outlined in red. For each isoform, the predicted binding residues are shown as sticks: residues in green are conserved at the functional level with PRKAG1, residues in red are not. AAKG-4 and AAKG-5 do not show conservation of AMP-binding residues with PRKAG1. AAKG-1-3 show high conservation of predicted key AMP-binding residues with human PRKAG1, and AAKG-2 is shown as an example. ) are required for normal responses to AMP, and contribute to normal fecundity and lifespan.ĪMP-binding sites within AAKG-2, AAKG-4, and AAKG-5 modelled using PyMOL. We show that in normal animals, three of these γ subunits ( Here, we genetically dissect the functional role of the different γ subunits in relation to physiology and lifespan. Despite the importance of the γ subunit, mostĪMPK research has focused on the catalytic α subunit. Modifying the ability of AMPKγ to bind adenine nucleotides could directly impact how effectively AMPK manages energy homeostasis. Have five different AMPKγ subunits and their primary amino acid sequence implies two different modes of AMP-binding. It is also regulated allosterically by the nucleotide AMP binding within the γ subunit. Active AMPK is characterised by phosphorylation of the α subunit. AMPK is a heterotrimeric protein consisting of α catalytic, β linker, and γ regulatory subunits. InĪMPK is important for controlling a multitude of functions including metabolism, reproductive health, and lifespan. In response to high AMP levels, AMPK promotes a metabolic shift towards increased catabolism and autophagy to restore cellular energy and maintain homeostasis. AMP-activated protein kinase (AMPK) is a key metabolic regulator which responds to changes in the AMP:ATP ratio within cells.
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