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PDBsum entry 2aao
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References listed in PDB file
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Key reference
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Title
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Structure of the regulatory apparatus of a calcium-Dependent protein kinase (cdpk): a novel mode of calmodulin-Target recognition.
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Authors
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V.Chandran,
E.J.Stollar,
K.Lindorff-Larsen,
J.F.Harper,
W.J.Chazin,
C.M.Dobson,
B.F.Luisi,
J.Christodoulou.
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Ref.
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J Mol Biol, 2006,
357,
400-410.
[DOI no: ]
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PubMed id
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Abstract
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Calcium-dependent protein kinases (CDPKs) are a class of calcium-binding sensory
proteins that are found in plants and certain protozoa, including the causative
agent of malaria, Plasmodium falciparum. CDPKs have diverse regulatory
functions, including involvement in the triggering of the lytic cycle of
malarial infection. CDPKs contain an autoinhibitory junction (J) region whose
calcium-dependent interaction with the tethered regulatory calmodulin-like
domain (CaM-LD) activates the catalytic kinase domain. We report here the X-ray
crystal structure of the J-CaM-LD region of CDPK from Arabidopsis thaliana
(AtCPK1), determined to 2.0 A resolution using multiple-wavelength anomalous
dispersion (MAD). The structure reveals a symmetric dimer of calcium-bound
J-CaM-LD with domain-swap interactions, in which the J region of one protomer
interacts extensively with the carboxy-terminal EF-hand domain (C-lobe) of the
partner protomer. However, as the J-CaM-LD is monomeric in solution, the
activated monomer was modelled to account for the intra-molecular recognition of
the two domains. While the J-CaM-LD segment mimics certain aspects of target
motif recognition by CaM other features are specific to CDPKs, in particular the
combination of the strong interaction between the N and C-lobes of the CaM-LD
and the exclusive use of only the C-lobe in the recognition of the covalently
tethered target region. Combined with our previous observations showing that
there is likely to be strong interactions between this tethered J region and the
CaM-LD even at basal Ca(2+) concentrations, the new structural data indicate
that the response to calcium of CDPKs is clearly unique among the CaM family.
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Figure 1.
Figure 1. (a) Schematic of the domain structure of CDPK.
The regulatory apparatus is comprised of the Junction region (J)
and the calmodulin-like domain (CaM-LD). (b) Ribbon diagram of
the crystal structure of the regulatory apparatus of CDPK
showing the homodimeric organization observed. The two molecules
are coloured in red and blue, respectively. The J region of each
monomer depicted in a darker colour is observed interacting with
the partner molecule in a domain swap interaction. The inset
depicts these interactions schematically. (c) Overlay of the
amino-terminal and carboxyl-terminal calcium-binding sub-domains
of the CaM-LD (N-lobe and C-lobe, respectively). The
root-mean-square deviation (RMSD) of C^α atoms for the overlay
is 0.9 Å. The models are complete except for residues
428–432, 556–562, 588–591 from protomer A and residues
428–432, 551–566, 588–591 from protomer B.
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Figure 3.
Figure 3. (a) Stereo view of the interaction of the J
region with the C-lobe of the CaM-LD. The J region is shown in
red and the C-lobe in blue. (b) A schematic summary of the key
interactions of the helical J region with the CaM-LD (boxed).
The J region interacts exclusively with the C-lobe.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
357,
400-410)
copyright 2006.
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