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PDBsum entry 4gje
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Contractile protein
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PDB id
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4gje
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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 structure of cardiac troponin c regulatory domain with bound cd2+ reveals a closed conformation and unique ion coordination.
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Authors
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X.L.Zhang,
G.F.Tibbits,
M.Paetzel.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2013,
69,
722-734.
[DOI no: ]
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PubMed id
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Abstract
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The amino-terminal domain of cardiac troponin C (cNTnC) is an essential Ca(2+)
sensor found in cardiomyocytes. It undergoes a conformational change upon Ca(2+)
binding and transduces the signal to the rest of the troponin complex to
initiate cardiac muscle contraction. Two classical EF-hand motifs (EF1 and EF2)
are present in cNTnC. Under physiological conditions, only EF2 binds Ca(2+); EF1
is a vestigial site that has lost its function in binding Ca(2+) owing to
amino-acid sequence changes during evolution. Proteins with EF-hand motifs are
capable of binding divalent cations other than calcium. Here, the crystal
structure of wild-type (WT) human cNTnC in complex with Cd(2+) is presented. The
structure of Cd(2+)-bound cNTnC with the disease-related mutation L29Q, as well
as a structure with the residue differences D2N, V28I, L29Q and G30D (NIQD),
which have been shown to have functional importance in Ca(2+) sensing at lower
temperatures in ectothermic species, have also been determined. The structures
resemble the overall conformation of NMR structures of Ca(2+)-bound cNTnC, but
differ significantly from a previous crystal structure of Cd(2+)-bound cNTnC in
complex with deoxycholic acid. The subtle structural changes observed in the
region near the mutations may play a role in the increased Ca(2+) affinity. The
1.4 Å resolution WT cNTnC structure, which is the highest resolution
structure yet obtained for cardiac troponin C, reveals a Cd(2+) ion coordinated
in the canonical pentagonal bipyramidal geometry in EF2 despite three residues
in the loop being disordered. A Cd(2+) ion found in the vestigial ion-binding
site of EF1 is coordinated in a noncanonical `distorted' octahedral geometry. A
comparison of the ion coordination observed within EF-hand-containing proteins
for which structures have been solved in the presence of Cd(2+) is presented. A
refolded WT cNTnC structure is also presented.
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