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Structures of the PKA RI alpha Holoenzyme with the FLHCC Driver J-PKAc alpha or Wild-Type PKAc alpha

  1. Author:
    Cao,Baohua
    Lu, Tsan-Wen
    Martinez Fiesco,Juliana
    Tomasini, Michael
    Fan,Lixin
    Simon, Sanford M.
    Taylor, Susan S.
    Zhang,Ping

  2. Author Address

    NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21701 USA.Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.Rockefeller Univ, Lab Cellular Biophys, 1230 York Ave, New York, NY 10021 USA.Leidos Biomed Res Inc, Small Angle Xray Scattering Core Facil, Ctr Canc Res, Natl Canc Inst,Frederick Natl Lab Canc Res, Frederick, MD USA.
    1. Year: 2019
    2. Date: MAY 7
    3. Epub Date: 2019 03 15
  2. Journal: Structure (London, England : 1993)
  3. CELL PRESS,
    1. 27
    2. 5
    3. Pages: 816-+
  5. Type of Article: Article
  6. ISSN: 0969-2126
  1. Abstract:

    Fibrolamellar hepatocellular carcinoma (FLHCC) is driven by J-PKAc alpha, a kinase fusion chimera of the J domain of DnaJB1 with PKAc alpha, the catalytic subunit of protein kinase A (PKA). Here we report the crystal structures of the chimeric fusion RI alpha(2):J-PKAc alpha(2) holoenzyme formed by J-PKAc alpha and the PKA regulatory (R) subunit RI alpha, and the wild-type (WT) RI alpha(2):PKAc alpha(2) holoenzyme. The chimeric and WT RI alpha holoenzymes have quaternary structures different from the previously solved WT RI beta and RII beta holoenzymes. The WT RI alpha holoenzyme showed the same configuration as the chimeric RI alpha(2):J-PKAc alpha(2) holoenzyme and a distinct second conformation. The J domains are positioned away from the symmetrical interface between the two RI alpha:J-PKAc alpha 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-PKAc alpha that drives FLHCC as well as the isoform specificity of PKA.

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External Sources

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  2. DOI: 10.1016/j.str.2019.03.001
  3. PMID: 30905674
  4. View record in Web of Science®
  5. WOS: 000467238900011

Library Notes

  1. Fiscal Year: FY2018-2019
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