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Accueil > Research > Research teams > NMR & Molecular Interactions > Presentation

NMR & Molecular Interactions

Présentation

Team’ website : http://groupe-rmn-modelisation.univ-lille1.fr/

Research interests :

We are interested in the structural and functional consequences of post-translational modifications (PTMs) on both intrinsically disordered and folded proteins. NMR spectroscopy is as a versatile emerging tool to study PTMs beyond the ability to detect/quantify PTM sites. The same sample can indeed be employed to map structural changes and functional interactions with other molecules. We are focusing on the deciphering of the complex phosphorylation code of the neuronal Tau protein and its implication in Alzheimer Disease. We additionally study at the molecular level acetylation and O-GlcNAcylation (O-ß-linked N-acetylglucosaminylation) of Tau, two PTMs that are involved either in the regulation of phosphorylation or in the control of Tau function/aggregation. We combine in vitro enzymatic reactions with recombinant enzymes to modify Tau, and Nuclear Magnetic Resonance spectroscopy to unravel the resulting modification pattern. Beyond the analytical capacity, this approach is followed by functional assays with the same samples to characterize protein-protein interactions (PPI). Small-molecule compounds that could interfere with Tau aggregation processes are further investigated both at the structural and functional levels. In addition to deciphering the complex biology of Tau, our methodology is also used in another biological system of interest. To replicate the Hepatitis C Virus (HCV) requires, in addition to its own proteins, the intervention of host cell factors. Among these cell factors the human Cyclophilin A (CypA) protein with its enzymatic peptidyl prolyl cis-trans isomerase activity is mandatory for efficient HCV replication and production of infectious particles. We are focusing on the deciphering of the structural and functional aspects resulting from the interaction between the human CypA and two HCV proteins : NS5A, a multifunctional protein for which no precise molecular activity has been identified, and NS5B, the viral RNA-dependent RNA polymerase.