Localization and quaternary structure of the PKA RIβ holoenzyme

Ronit Ilouz, José Bubis, Jian Wu, Yun Young Yim, Michael S. Deal, Alexandr P. Kornev, Yuliang Ma, Donald K. Blumenthal, Susan S. Taylor

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Specificity for signaling by cAMP-dependent protein kinase (PKA) is achieved by both targeting and isoform diversity. The inactive PKA holoenzyme has two catalytic (C) subunits and a regulatory (R) subunit dimer (R 2:C2). Although the RIα, RIIα, and RIIβ isoforms are well studied, little is known about RIβ. We show here that RIβ is enriched selectively in mitochondria and hypothesized that its unique biological importance and functional nonredundancy will correlate with its structure. Small-angle X-ray scattering showed that the overall shape of RIβ2:C2 is different from its closest homolog, RIα2:C2. The full-length RIβ2:C 2 crystal structure allows us to visualize all the domains of the PKA holoenzyme complex and shows how isoform-specific assembly of holoenzyme complexes can create distinct quaternary structures even though the R 1:C1 heterodimers are similar in all isoforms. The creation of discrete isoform-specific PKA holoenzyme signaling "foci" paves the way for exploring further biological roles of PKA RIβ and establishes a paradigm for PKA signaling.

Original languageEnglish
Pages (from-to)12443-12448
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number31
DOIs
StatePublished - 31 Jul 2012
Externally publishedYes

Funding

FundersFunder number
National Institute of General Medical SciencesR01GM034921
National Institute of Diabetes and Digestive and Kidney DiseasesP01DK054441

    Keywords

    • Allostery
    • Signal transduction
    • Structural biology

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