Structural highlights
6byr is a 4 chain structure with sequence from Bovin and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| NonStd Res: | , |
| Gene: | PRKACA, PKACA (HUMAN), PRKAR1A (BOVIN) |
| Activity: | cAMP-dependent protein kinase, with EC number 2.7.11.11 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[DNJB1_HUMAN] Interacts with HSP70 and can stimulate its ATPase activity. Stimulates the association between HSC70 and HIP. [KAP0_BOVIN] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.
Publication Abstract from PubMed
Fibrolamellar hepatocellular carcinoma (FLHCC) is driven by J-PKAcalpha, a kinase fusion chimera of the J domain of DnaJB1 with PKAcalpha, the catalytic subunit of protein kinase A (PKA). Here we report the crystal structures of the chimeric fusion RIalpha2:J-PKAcalpha2 holoenzyme formed by J-PKAcalpha and the PKA regulatory (R) subunit RIalpha, and the wild-type (WT) RIalpha2:PKAcalpha2 holoenzyme. The chimeric and WT RIalpha holoenzymes have quaternary structures different from the previously solved WT RIbeta and RIIbeta holoenzymes. The WT RIalpha holoenzyme showed the same configuration as the chimeric RIalpha2:J-PKAcalpha2 holoenzyme and a distinct second conformation. The J domains are positioned away from the symmetrical interface between the two RIalpha:J-PKAcalpha 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-PKAcalpha that drives FLHCC as well as the isoform specificity of PKA.
Structures of the PKA RIalpha Holoenzyme with the FLHCC Driver J-PKAcalpha or Wild-Type PKAcalpha.,Cao B, Lu TW, Martinez Fiesco JA, Tomasini M, Fan L, Simon SM, Taylor SS, Zhang P Structure. 2019 Mar 15. pii: S0969-2126(19)30079-6. doi:, 10.1016/j.str.2019.03.001. PMID:30905674[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cao B, Lu TW, Martinez Fiesco JA, Tomasini M, Fan L, Simon SM, Taylor SS, Zhang P. Structures of the PKA RIalpha Holoenzyme with the FLHCC Driver J-PKAcalpha or Wild-Type PKAcalpha. Structure. 2019 Mar 15. pii: S0969-2126(19)30079-6. doi:, 10.1016/j.str.2019.03.001. PMID:30905674 doi:http://dx.doi.org/10.1016/j.str.2019.03.001
