5'-AMP-activated protein kinase subunit gamma (AMPK gamma)

The 5'-AMP-activated protein kinase (AMPK) gamma subunit is the regulatory component of the AMPK heterotrimeric complex, acting as a sophisticated sensor for cellular energy status. It contains four cystathionine beta-synthase (CBS) domains that form two Bateman domains; specifically, the CBS-3 domain is one of the primary sites for the competitive binding of AMP, ADP, and ATP (Hardie, 2012, PubMed: 22349066). When cellular energy is low, the binding of AMP or ADP to these CBS domains induces a conformational change that allosterically activates the catalytic alpha subunit and prevents its dephosphorylation at Thr172, thereby maintaining the enzyme in an active state (Xiao et al., 2007, PubMed: 17851521). This activation triggers a shift from anabolic to catabolic metabolism to restore ATP levels. Mutations in the gamma subunit, particularly the PRKAG2 isoform, are clinically significant as they lead to abnormal glycogen accumulation and cardiac conditions such as Wolff-Parkinson-White syndrome and hypertrophic cardiomyopathy (Arad et al., 2002, PubMed: 12050335). Pharmacological targeting of the CBS domains, including CBS-3, is a major area of research for treating metabolic disorders like type 2 diabetes and obesity.

Other names

PRKAGAMPK gamma subunitAMP-activated protein kinase regulatory subunitCystathionine beta-synthase domain-containing subunit of AMPK

Allosteric activation of the AMPK complex and protection of the alpha-subunit Thr172 residue from dephosphorylation through competitive nucleotide binding at CBS domains.