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PDBsum entry 1sbj
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Contractile protein, structural protein
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PDB id
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1sbj
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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 mg2+-Loaded c-Lobe of cardiac troponin c bound to the n-Domain of cardiac troponin i: comparison with the ca2+-Loaded structure.
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Authors
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N.L.Finley,
J.W.Howarth,
P.R.Rosevear.
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Ref.
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Biochemistry, 2004,
43,
11371-11379.
[DOI no: ]
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PubMed id
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Abstract
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Cardiac troponin C (cTnC) is the Ca(2+)-binding component of the troponin
complex and, as such, is the Ca(2+)-dependent switch in muscle contraction. This
protein consists of two globular lobes, each containing a pair of EF-hand
metal-binding sites, connected by a linker. In the N lobe, Ca(2+)-binding site I
is inactive and Ca(2+)-binding site II is primarily responsible for initiation
of muscle contraction. The C lobe contains Ca(2+)/Mg(2+)-binding sites III and
IV, which bind Mg(2+) with lower affinity and play a structural as well as a
secondary role in modulating the Ca(2+) signal. To understand the structural
consequences of Ca(2+)/Mg(2+) exchange in the C lobe, we have determined the NMR
solution structure of the Mg(2+)-loaded C lobe, cTnC(81-161), in a complex with
the N domain of cardiac troponin I, cTnI(33-80), and compared it with a refined
Ca(2+)-loaded structure. The overall tertiary structure of the Mg(2+)-loaded C
lobe is very similar to that of the refined Ca(2+)-loaded structure as evidenced
by the root-mean-square deviation of 0.94 A for all backbone atoms. While
metal-dependent conformational changes are minimal, substitution of Mg(2+) for
Ca(2+) is characterized by condensation of the C-terminal portion of the
metal-binding loops with monodentate Mg(2+) ligation by the conserved Glu at
position 12 and partial closure of the cTnI hydrophobic binding cleft around
site IV. Thus, conformational plasticity in the Ca(2+)/Mg(2+)-dependent binding
loops may represent a mechanism to modulate C-lobe cTnC interactions with the N
domain of cTnI.
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