Normand Mousseau
Professeur de physique et titulaire de la Chaire UdeM
Matériaux complexes, énergie et ressources naturelles

Vincent Binette

Étudiant au doctorat

Projets de recherche

  • Développement d’une nouvelle paramétrisation de potentiels de la famille OPEP
  • Couplage avec la méthode ART
  • Étude par la méthode des répliques du terminal N de HTT sur une membrane.


Articles publiés dans le groupe

  • V. Binette, S. Côté, N. Mousseau, Free energy Landscape of the Amino-terminal Fragment of Huntingtin in Aqueous Solution, Biophysical Journal (2016).
    Mots-clés : amyloide.

  • S. Côté, V. Binette, E.  S. Salnikov, B. Bechinger, N. Mousseau, Probing the Huntingtin 1-17 Membrane Anchor on a Phospholipid Bilayer by Using All-Atom Simulations, Biophysical Journal 108, 1187-1198 (2015).
    Résumé : Mislocalization and aggregation of the huntingtin protein are related to Huntington?s disease. Its first exon?more specifically the first 17 amino acids (Htt17)?is crucial for the physiological and pathological functions of huntingtin. It regulates huntingtin?s activity through posttranslational modifications and serves as an anchor to membrane-containing organelles of the cell. Recently, structure and orientation of the Htt17 membrane anchor were determined using a combined solution and solid-state NMR approach. This prompted us to refine this model by investigating the dynamics and thermodynamics of this membrane anchor on a POPC bilayer using all-atom, explicit solvent molecular dynamics and Hamiltonian replica exchange. Our simulations are combined with various experimental measurements to generate a high-resolution atomistic model for the huntingtin Htt17 membrane anchor on a POPC bilayer. More precisely, we observe that the single α-helix structure is more stable in the phospholipid membrane than the NMR model obtained in the presence of dodecylphosphocholine detergent micelles. The resulting Htt17 monomer has its hydrophobic plane oriented parallel to the bilayer surface. Our results further unveil the key residues interacting with the membrane in terms of hydrogen bonds, salt-bridges, and nonpolar contributions. We also observe that Htt17 equilibrates at a well-defined insertion depth and that it perturbs the physical properties?order parameter, thickness, and area per lipid?of the bilayer in a manner that could favor its dimerization. Overall, our observations reinforce and refine the NMR measurements on the Htt17 membrane anchor segment of huntingtin that is of fundamental importance to its biological functions.
    Mots-clés : amyloide.
mardi 1er juillet 2014

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