Laëtita Bourgeat defends her PhD on Dec. 9, 2020 at 1:45 PM.
Place : visio conference only,
Rapporteur-e-s : CHOMILIER Jacques, PREVOST Chantal
Examinateur-rice-s : BARBI Maria, CORREIA Natalia, JOLY Laurent, RAHBE Yvan
Directeur-rice-s de thèse : LESIEUR Claire, SERGHEI Anatoli
Abstract :
Proteins are highly studied molecules because of their different roles and the impact of their dysfunction on the state of health of living organisms. In recent years, studies have shown that a protein doesn’t have a single conformation (3D structure) to respond to its function, but several. As of today, different techniques exist to detect and determine the protein conformation, no technique can reconstitute all the conformations studied by a protein by individually screening the conformations that constitute it.
The work of this memory is to determine if the combination of nanoconfinement and broadband dielectric spectroscopy can be used to screen different protein conformations and thus try to reconstruct the conformational set of a protein. Nanoconfinement is used to reduce the conformational heterogeneity that exists within a population on a macroscopic scale. Broadband dielectric spectroscopy characterizes molecular dynamics which are related to protein conformation. This method can therefore be used as a tool to study the impact of a change in conformation on molecular dynamics.
My thesis work demonstrated that the combination of nanoconfinement and broadband dielectric spectroscopy could be used to screen different protein conformations by modifying the dimensions of the confinement. Different conformations of pentameric B subunits of cholera toxin (CtxB5), heat labile enterotoxin (LTB5), and lysozyme have been observed. The differences between the dielectric signals of the two toxins reveal local structures with distinct dynamics, while the differences with lysozyme reveal global structures with distinct dynamics. These results open perspectives for diagnosing structural and / or dynamic impacts linked to mutations, the implication of which in the development of diseases or the design of drugs can be explored within the framework of personalized therapies.
Key Words : protein, nanoconfinement, broadband dielectric spectroscopy, conformation, molecular dynamics, screen
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