Structures of the PKA RIα Holoenzyme with the FLHCC Driver J-PKAcα or Wild-Type PKAcα.

ABSTRACT: Fibrolamellar hepatocellular carcinoma (FLHCC) is driven by J-PKAcα, a kinase fusion chimera of the J domain of DnaJB1 with PKAcα, the catalytic subunit of protein kinase A (PKA). Here we report the crystal structures of the chimeric fusion RIα₂:J-PKAcα₂ holoenzyme formed by J-PKAcα and the PKA regulatory (R) subunit RIα, and the wild-type (WT) RIα₂:PKAcα₂ holoenzyme. The chimeric and WT RIα holoenzymes have quaternary structures different from the previously solved WT RIβ and RIIβ holoenzymes. The WT RIα holoenzyme showed the same configuration as the chimeric RIα₂:J-PKAcα₂ holoenzyme and a distinct second conformation. The J domains are positioned away from the symmetrical interface between the two RIα:J-PKAcα heterodimers

SUBMITTER: Cao B 

PROVIDER: S-EPMC6506387 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature