Contribution of troponin-I to the regulation of cardiac muscle

Mitchell, Wayne William Alfred (2011). Contribution of troponin-I to the regulation of cardiac muscle. University of Birmingham. Ph.D.

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Abstract

Troponin-I (TnI) is one of the three components that makes up the troponin complex, which along with tropomyosin regulates striated muscle contraction. The cardiac isoform of TnI (cTnI) has a ~30 residue N-terminal extension, which contains two serines (Ser22/23) that become phosphorylated by protein kinase A upon \(\beta\)-adrenergic stimulation. However, the function of the N-terminus of cTnI remains unclear. Questions also remain about the function of the C-terminal region of cTnI, although its importance has been demonstrated by mutagenesis and deletion studies. With the use of \(^1\)H nuclear magnetic resonance (NMR) spectroscopy it has been possible to investigate the F-actin binding capability of the N-terminal and C-terminal regions of cTnI. The extreme C-terminal region of (human) hcTnI was demonstrated to interact with F-actin and assist in the localisation of hcTnI to the thin filament. This thesis also demonstrates that a region of the N-terminus of hcTnI, close to the site of phosphorylation, interacts with F-actin and that this interaction was maintained upon monophosphorylation. The interaction between F-actin and the N-terminus of hcTnI was also detected when in a complex with hcTnC. The conclusions suggest a mechanism for regulating contractile activity in a manner specific to cardiac TnI.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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