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Localization and quaternary structure of the PKA RI? holoenzyme.


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):C(2)). Although the RI?, RII?, and RII? isoforms are well studied, little is known about RI?. We show here that RI? 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 RI?(2):C(2) is different from its closest homolog, RI?(2):C(2). The full-length RI?(2):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):C(1) 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 RI? and establishes a paradigm for PKA signaling.

SUBMITTER: Ilouz R 

PROVIDER: S-EPMC3411989 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Localization and quaternary structure of the PKA RIβ holoenzyme.

Ilouz Ronit R   Bubis José J   Wu Jian J   Yim Yun Young YY   Deal Michael S MS   Kornev Alexandr P AP   Ma Yuliang Y   Blumenthal Donald K DK   Taylor Susan S SS  

Proceedings of the National Academy of Sciences of the United States of America 20120713 31


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):C(2)). 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-a  ...[more]

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2017-08-10 | GSE102461 | GEO