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PDBsum entry 2w73
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Metal binding protein
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PDB id
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2w73
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References listed in PDB file
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Key reference
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Title
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Domain swapping and different oligomeric states for the complex between calmodulin and the calmodulin-Binding domain of calcineurin a.
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Authors
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V.Majava,
P.Kursula.
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Ref.
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Plos One, 2009,
4,
e5402.
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PubMed id
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Abstract
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BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that
engages in regulatory interactions with a large number of cellular proteins.
Previously, a unique mode of CaM target recognition has been observed in the
crystal structure of a complex between CaM and the CaM-binding domain of
calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution
crystal structure of a complex between CaM and the CaM-binding domain of
calcineurin A in a novel crystal form, which shows a dimeric assembly of
calmodulin, as observed before in the crystal state. We note that the
conformation of CaM in this complex is very similar to that of unliganded CaM,
and a detailed analysis revels that the CaM-binding motif in calcineurin A is of
a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show
that the complex is fully monomeric in solution, and a structure of a
canonically collapsed CaM-peptide complex can easily be fitted into the SAXS
data. This result is also supported by size exclusion chromatography, where the
addition of the ligand peptide decreases the apparent size of CaM. In addition,
we studied the energetics of binding by isothermal titration calorimetry and
found them to closely resemble those observed previously for ligand peptides
from CaM-dependent kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that
CaM can also form a complex with the CaM-binding domain of calcineurin in a 1
ratio 1 stoichiometry, in addition to the previously observed 2 ratio 2
arrangement in the crystal state. At the structural level, going from 2 ratio 2
association to two 1 ratio 1 complexes will require domain swapping in CaM,
accompanied by the characteristic bending of the central linker helix between
the two lobes of CaM.
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