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Structure and dynamics of biomolecules: probing muscle regulation, prion protein unfolding, and drug insertion into DNA by nuclear magnetic resonance spectroscopy Open Access


Other title
Type of item
Degree grantor
University of Alberta
Author or creator
Julien, Olivier
Supervisor and department
Sykes, Brian D. (Biochemistry)
Examining committee member and department
Westaway, David (Medicine)
Spyracopoulos, Leo (Biochemistry)
Sönnichsen, Frank (University of Kiel)
Young,Howard S. (Biochemistry)
Department of Biochemistry

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Nuclear magnetic resonance (NMR) spectroscopy is a powerful approach to study the structure and dynamics of macromolecules in a close-to-native solution environment. In the present thesis I present my investigation of protein and nucleic acid structure and dynamics in a wide variety of biological systems using NMR spectroscopy. The center of attention of the Sykes laboratory for the last 35 years has been the role of the Troponin complex in the regulation of muscle contraction. Accordingly, the main focus of this thesis is the study of this important nano-machine, and how its structure and dynamics regulate its biological function. In Chapter II, the perturbation of Troponin C’s structure and dynamics by the attachment of two different bifunctional rhodamine probes is investigated. In Chapter III, the dynamics and position of the bifunctional rhodamine probe when attached on the C helix of Troponin C is studied. In Chapter IV, the structure and dynamics of tryptophan mutants of Troponin C is reported. In Chapter V, the effect of the co-solvent trifluoroethanol on the tryptophan side chain position of mutant F77W of the N-domain of Troponin C is examined. In the following chapter, Chapter VI, the structure and dynamics of a Troponin C – Troponin I chimera is studied using NMR spectroscopy and molecular dynamics simulations to assess the presence or absence of an intrinsically disordered region in Troponin I, and to assess the validity of the flycasting mechanism proposed to regulate muscle contraction. In Chapter VII and VIII, a different topic is introduced. The structural changes occurring during the denaturation process of the bovine prion protein are monitored using NMR spectroscopy to gain insights into the protein misfolding process that causes diseases. In Chapter IX, the structural impact of inserting nucleoside phosphonates into DNA are examined by reporting the NMR structure of a DNA dodecamer duplex containing the modified nucleoside Cidofovir at position 7.
License granted by Olivier Julien ( on 2011-04-01T19:09:03Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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