N3A motifs in RIβ mediate allosteric crosstalk between cAMP and ATP in PKA activation.

ABSTRACT: The RIβ subunit of cAMP-dependent protein kinase (PKA) is highly expressed in the brain, yet it remains the least studied of the PKA regulatory subunits (R). As pathologic variants of its gene are increasingly implicated in neurodevelopmental disorders, neurodegeneration, and cancer, gaining more information about the structure/function of RIβ, and how it differs from RIα, has become increasingly important. We previously reported the structure of the RIβ₂C₂ holoenzyme, which revealed a novel conformation where ATP binding was stabilized by a head-to-head anti-parallel packing of the C-tail wrapped around the N-lobe of the catalytic subunit (C). Although visible, the Dimerization/Docking Domain was poorly folded and reduced. Since RIβ is oxidized in brain tissues, we a

SUBMITTER: Wu J 

PROVIDER: S-EPMC12535202 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature