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J Biol Chem. 2002 Nov 1;277(44):41795-801. Epub 2002 Aug 30.

Structural consequences of cardiac troponin I phosphorylation.

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School of Biosciences, University of Birmingham, Edgbaston, United Kingdom.


beta-Adrenergic stimulation of the heart results in bisphosphorylation of the N-terminal extension of cardiac troponin I (TnI). Bisphosphorylation of TnI reduces the affinity of the regulatory site on troponin C (TnC) for Ca(2+) by increasing the rate of Ca(2+) dissociation. What remains unclear is how the phosphorylation signal is transmitted from one subunit of troponin to another. We have produced a series of mutations in the N-terminal extension of TnI designed to further our understanding of the mechanisms involved. The ability of phosphorylation of the mutant TnIs to affect Ca(2+) sensitivity has been assessed. We find that the Pro residues found in a conserved (Xaa-Pro)(4) motif N-terminal to the phosphorylation sites are not required for the effect of the N-terminal extension on Ca(2+) binding in the presence or absence of phosphorylation. Our experiments also reveal that the full effects of phosphorylation are seen even when residues 1-15 of TnI are deleted. If further residues are removed, not only does the effect of phosphorylation diminish but deletion of the N-terminal extension mimics phosphorylation. We propose that TnI residues 16-29 bind to TnC stabilizing the "open" Ca(2+)-bound state. Phosphorylation (or deletion) prevents this binding, accelerating Ca(2+) release.

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