Fractionation factors reveal hidden frustration in an ancient allosteric module

Protein kinase G (PKG) is an essential regulator of eukaryotic cyclic guanosine monophosphate (cGMP)-dependent intracellular signaling, controlling pathways that are often distinct from those regulated by cyclic adenosine monophosphate (cAMP). Specifically, the C-terminal cyclic-nucleotide-binding domain (CNB-B) of PKG has emerged as a critical module to control allostery and cGMP-selectivity in PKG. While key contributions to the …