6BYS

Structures of the PKA RI alpha holoenzyme with the FLHCC driver J-PKAc alpha or native PRKAc alpha

Summary for 6BYS

• Entry DOI: 10.2210/pdb6bys/pdb
• Descriptor: cAMP-dependent protein kinase catalytic subunit alpha, cAMP-dependent protein kinase type I-alpha regulatory subunit (2 entities in total)
• Functional Keywords: signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 334295.10

Authors

Cao, B.,Lu, T.W.,Martinez Fiesco, J.A.,Tomasini, M.,Fan, L.,Simon, S.M.,Taylor, S.S.,Zhang, P. (deposition date: 2017-12-21, release date: 2019-04-03, Last modification date: 2024-11-06)

Primary citation

Cao, B.,Lu, T.W.,Martinez Fiesco, J.A.,Tomasini, M.,Fan, L.,Simon, S.M.,Taylor, S.S.,Zhang, P.
Structures of the PKA RI alpha Holoenzyme with the FLHCC Driver J-PKAc alpha or Wild-Type PKAc alpha.
Structure, 27:816-, 2019

PubMed 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 RIα:J-PKAcα holoenzyme formed by J-PKAcα and the PKA regulatory (R) subunit RIα, and the wild-type (WT) RIα:PKAcα 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 RIα:J-PKAcα holoenzyme and a distinct second conformation. The J domains are positioned away from the symmetrical interface between the two RIα:J-PKAcα heterodimers in the chimeric fusion holoenzyme and are highly dynamic. The structural and dynamic features of these holoenzymes enhance our understanding of the fusion chimera protein J-PKAcα that drives FLHCC as well as the isoform specificity of PKA.

PubMed: 30905674
DOI: 10.1016/j.str.2019.03.001

Experimental method

X-RAY DIFFRACTION (4.75 Å)