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Contribution of troponin-I to the regulation of cardiac muscle

Mitchell, Wayne William Alfred (2011)
Ph.D. thesis, University of Birmingham.

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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:Ph.D. thesis.
Supervisor(s):Patchell, Val and Levine, Barry
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:College of Medical and Dental Sciences
Subjects:R Medicine (General)
RC Internal medicine
Institution:University of Birmingham
ID Code:1505
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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