Interacciones proteína-membrana: una aproximación estructural por RMN utilizando sistemas modelo

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Universidad Complutense de Madrid
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Nuclear Magnetic Resonance (NMR) spectroscopy has applications in multiple areas of science, especially in chemistry, biochemistry and biomedicine. NMR is a very versatile technique for determining the structure, dynamics and interactions of organic molecules and biomolecules in solution. Also, NMR is a technique experimenting rapid and continuous advances, both by instrument technology and by the development of new experimental techniques. In this context, chapter II of this Thesis addresses the development of a new pulse sequence, which provides a new tool for the study of intrinsically disordered proteins (IDPs). This is of great relevance because of the complex conformational behavior of IDPs, and the increasing number of known IDPs. Meanwhile, chapters III-V exploit the NMR versatility for the characterization and structural determination of biomolecules and their interactions. Structural characterization and dynamics of these interactions with atomic resolution is essential to understand their functionality within the cell. This information can be of practical use, for instance, in the development of new drugs and new therapeutic strategies for the treatment of various diseases. Within this broad field, chapters III-IV aim to characterize the interactions of two particular biological systems using both protein and membrane mimetics. The two systems studied include boomerang peptides as heparin-binding models, in chapter III, and peptides derived from the gp41 protein in presence of simple mimetic of membrane environments, an apolar medium and micelles, in chapter IV. In chapter V, a complete characterization of a circularly permutated onconasa variant, ONCFLG zymogen, is performed. The internal dynamics and the conformational stability at the residue level are determined. The findings on these systems has provided us additional information to that available before starting this work, which allow us to derive structure-function implications. In brief, the work done in this Thesis has provided us a new experimental NMR method applicable to intrinsically disordered protein, an emerging area in the protein field, and new data about three biological systems, which has improved our understanding of the molecular basis of their biological functions.
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular I, leída el 04-06-2014
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