Structural consequences of cardiac troponin I phosphorylation

Douglas Ward, Michael Cornes, Ian Trayer

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)41795-41801
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number44
Early online date30 Aug 2002
DOIs
Publication statusPublished - 25 Oct 2002

Fingerprint

Dive into the research topics of 'Structural consequences of cardiac troponin I phosphorylation'. Together they form a unique fingerprint.

Cite this