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PDBsum entry 3pvb
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References listed in PDB file
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Key reference
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Title
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Realizing the allosteric potential of the tetrameric protein kinase a riα holoenzyme.
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Authors
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A.J.Boettcher,
J.Wu,
C.Kim,
J.Yang,
J.Bruystens,
N.Cheung,
J.K.Pennypacker,
D.A.Blumenthal,
A.P.Kornev,
S.S.Taylor.
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Ref.
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Structure, 2011,
19,
265-276.
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PubMed id
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Abstract
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PKA holoenzymes containing two catalytic (C) subunits and a regulatory (R)
subunit dimer are activated cooperatively by cAMP. While cooperativity involves
the two tandem cAMP binding domains in each R-subunit, additional cooperativity
is associated with the tetramer. Of critical importance is the flexible linker
in R that contains an inhibitor site (IS). While the IS becomes ordered in the
R:C heterodimer, the overall conformation of the tetramer is mediated largely by
the N-Linker that connects the D/D domain to the IS. To understand how the
N-Linker contributes to assembly of tetrameric holoenzymes, we engineered a
monomeric RIα that contains most of the N-Linker, RIα(73-244), and
crystallized a holoenzyme complex. Part of the N-linker is now ordered by
interactions with a symmetry-related dimer. This complex of two symmetry-related
dimers forms a tetramer that reveals novel mechanisms for allosteric regulation
and has many features associated with full-length holoenzyme. A model of the
tetrameric holoenzyme, based on this structure, is consistent with previous
small angle X-ray and neutron scattering data, and is validated with new SAXS
data and with an RIα mutation localized to a novel interface unique to the
tetramer.
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