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PDBsum entry 3j4r
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230 a.a.
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382 a.a.
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325 a.a.
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References listed in PDB file
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Key reference
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Title
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Intrinsic disorder within an akap-Protein kinase a complex guides local substrate phosphorylation.
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Authors
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F.D.Smith,
S.L.Reichow,
J.L.Esseltine,
D.Shi,
L.K.Langeberg,
J.D.Scott,
T.Gonen.
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Ref.
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Elife, 2013,
2,
e01319.
[DOI no: ]
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PubMed id
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Abstract
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Anchoring proteins sequester kinases with their substrates to locally
disseminate intracellular signals and avert indiscriminate transmission of these
responses throughout the cell. Mechanistic understanding of this process is
hampered by limited structural information on these macromolecular complexes.
A-kinase anchoring proteins (AKAPs) spatially constrain phosphorylation by
cAMP-dependent protein kinases (PKA). Electron microscopy and three-dimensional
reconstructions of type-II PKA-AKAP18γ complexes reveal hetero-pentameric
assemblies that adopt a range of flexible tripartite configurations.
Intrinsically disordered regions within each PKA regulatory subunit impart the
molecular plasticity that affords an ∼16 nanometer radius of motion to the
associated catalytic subunits. Manipulating flexibility within the PKA
holoenzyme augmented basal and cAMP responsive phosphorylation of
AKAP-associated substrates. Cell-based analyses suggest that the catalytic
subunit remains within type-II PKA-AKAP18γ complexes upon cAMP elevation. We
propose that the dynamic movement of kinase sub-structures, in concert with the
static AKAP-regulatory subunit interface, generates a solid-state signaling
microenvironment for substrate phosphorylation. DOI:
http://dx.doi.org/10.7554/eLife.01319.001.
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