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PDBsum entry 1ap4
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Calcium-binding
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PDB id
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1ap4
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References listed in PDB file
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Key reference
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Title
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Calcium-Induced structural transition in the regulatory domain of human cardiac troponin c.
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Authors
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L.Spyracopoulos,
M.X.Li,
S.K.Sia,
S.M.Gagné,
M.Chandra,
R.J.Solaro,
B.D.Sykes.
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Ref.
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Biochemistry, 1997,
36,
12138-12146.
[DOI no: ]
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PubMed id
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Abstract
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While calcium binding to troponin C (TnC) triggers the contraction of both
skeletal and cardiac muscle, there is clear evidence that different mechanisms
may be involved. For example, activation of heart myofilaments occurs with
binding to a single regulatory site on TnC, whereas activation of fast skeletal
myofilaments occurs with binding to two regulatory sites. The physiological
difference between activation of cardiac and skeletal myofilaments is not
understood at the molecular level due to a lack of structural details for the
response of cardiac TnC to calcium. We determined the solution structures of the
apo and calcium-saturated regulatory domain of human cardiac TnC by using
multinuclear, multidimensional nuclear magnetic resonance spectroscopy. The
structure of apo human cardiac TnC is very similar to that of apo turkey
skeletal TnC even though there are critical amino acid substitutions in site I.
In contrast to the case with the skeletal protein, the calcium-induced
conformational transition in the cardiac regulatory domain does not involve an
"opening" of the regulatory domain, and the concomitant exposure of a
substantial hydrophobic surface area. This result has important implications
with regard to potential unique aspects of the interaction of cardiac TnC with
cardiac troponin I and of modification of cardiac myofilament regulation by
calcium-sensitizer drugs.
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