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PDBsum entry 1a03
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Calcium-binding protein
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PDB id
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1a03
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The three-Dimensional structure of ca(2+)-Bound calcyclin: implications for ca(2+)-Signal transduction by s100 proteins.
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Authors
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M.Sastry,
R.R.Ketchem,
O.Crescenzi,
C.Weber,
M.J.Lubienski,
H.Hidaka,
W.J.Chazin.
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Ref.
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Structure, 1998,
6,
223-231.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Calcyclin is a member of the S100 subfamily of EF-hand
Ca(2+)-binding proteins. This protein has implied roles in the regulation of
cell growth and division, exhibits deregulated expression in association with
cell transformation, and is found in high abundance in certain breast cancer
cell lines. The novel homodimeric structural motif first identified for apo
calcyclin raised the possibility that S100 proteins recognize their targets in a
manner that is distinctly different from that of the prototypical EF-hand Ca2+
sensor, calmodulin. The NMR solution structure of Ca(2+)-bound calcyclin has
been determined in order to identify Ca(2+)-induced structural changes and to
obtain insights into the mechanism of Ca(2+)-triggered target protein
recognition. RESULTS: The three-dimensional structure of Ca(2+)-bound calcyclin
was calculated with 1372 experimental constraints, and is represented by an
ensemble of 20 structures that have a backbone root mean square deviation of 1.9
A for the eight helices. Ca(2+)-bound calcyclin has the same symmetric
homodimeric fold as observed for the apo protein. The helical packing within the
globular domains and the subunit interface also change little upon Ca2+ binding.
A distinct homology was found between the Ca(2+)-bound states of the calcyclin
subunit and the monomeric S100 protein calbindin D9k. CONCLUSIONS: Only very
modest Ca(2+)-induced changes are observed in the structure of calcyclin, in
sharp contrast to the domain-opening that occurs in calmodulin and related
Ca(2+)-sensor proteins. Thus, calcyclin, and by inference other members of the
S100 family, must have a different mode for transducing Ca2+ signals and
recognizing target proteins. This proposal raises significant questions
concerning the purported roles of S100 proteins as Ca2+ sensors.
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Figure 2.
Figure 2. Comparison of the three-dimensional structures of
calcyclin and calbindin D[9k] in the Ca^2+-bound state. Overview
of calbindin D[9k] (a) and the calcyclin subunit (b),
highlighting the conserved residues in the hydrophobic core
(cyan). The two structures were first overlaid by best-fit
superposition of the backbone atoms of helices I, II and IV,
then separated for viewing. (c) Stereo close-up view of the
conserved hydrophobic residues at the interface between helices
I and IV, showing the similarity in the packing of corresponding
sidechains. The structures were overlaid by best-fit
superposition of the backbone atoms of helices I and IV.
Calbindin D[9k] is shown in yellow and calcyclin is in salmon;
the sidechains are labeled for calcyclin only. The coordinates
for calbindin D[9k] were obtained from the Brookhaven PDB
(accession code 2BCB). (Figure prepared using Insight II
[Version 95.0; MSI, San Diego].)
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
223-231)
copyright 1998.
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Secondary reference #1
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Title
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1h nmr assignments of apo calcyclin and comparative structural analysis with calbindin d9k and s100 beta.
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Authors
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B.C.Potts,
G.Carlström,
K.Okazaki,
H.Hidaka,
W.J.Chazin.
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Ref.
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Protein Sci, 1996,
5,
2162-2174.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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The structure of calcyclin reveals a novel homodimeric fold for s100 ca(2+)-Binding proteins.
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Authors
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B.C.Potts,
J.Smith,
M.Akke,
T.J.Macke,
K.Okazaki,
H.Hidaka,
D.A.Case,
W.J.Chazin.
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Ref.
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Nat Struct Biol, 1995,
2,
790-796.
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PubMed id
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Secondary reference #3
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Title
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Erratum. The structure of calcyclin reveals a novel homodimeric fold for s100 ca(2+)-Binding proteins
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Authors
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B.C.Potts,
J.Smith,
M.Akke,
T.J.Macke,
K.Okazaki,
H.Hidaka,
D.A.Case,
W.J.Chazin.
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Ref.
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nat struct biol, 1995,
2,
912.
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Secondary reference #4
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Title
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A calcium-Binding protein from rabbit lung cytosol identified as the product of growth-Regulated gene (2a9) and its binding proteins.
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Authors
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H.Tokumitsu,
R.Kobayashi,
H.Hidaka.
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Ref.
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Arch Biochem Biophys, 1991,
288,
202-207.
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PubMed id
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Secondary reference #5
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Title
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A calcium-Binding protein from rabbit lung cytosol identified as the product of growth-Regulated gene (2a9) and its binding proteins.
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Authors
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H.Tokumitsu,
R.Kobayashi,
H.Hidaka.
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Ref.
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Arch Biochem Biophys, 1991,
291,
401.
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PubMed id
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