"Membrane-Assisted Dynamic Protein-Protein Interactions by NMR" Tuesday May 15th 2018

Le Professeur A. Ramamoorthy de l'Université de Michigan donnera un séminaire intitulé  "Membrane-Assisted Dynamic Protein-Protein Interactions by NMR" le mardi 15 mai à 12h30, salle 101, tours 23-24.

Résumé :
In spite of the recent developments in structural biology, membrane proteins continue to pose tremendous challenges to most biophysical techniques. A major area of research in my group is focused on the development of NMR techniques to study the dynamic structural interactions between membrane bound proteins such as cytochrome b5, cytochrome P450 and cytochrome P450-reductase.[1,2] Strategies to study the dynamic structures of these challenging systems and also on the electron transfer mechanism that enables P450 enzymatic function will be presented in the first half of my talk. A variety of DNP-MAS and oriented solid-state NMR approaches to measure the transmembrane-transmembrane interactions will be highlighted. The advantages of protein-based, peptide-based and a newly designed polymer-based nanodiscs to study membrane proteins and amyloid proteins will be discussed.[3] A complete characterization and the unique magnetic-aligning feature of polymer-based macrodiscs, and the feasibility of solid-state NMR experiments will also be presented.

My research group has also been investigating the high-resolution structures of early amyloid intermediates, amyloid-membrane interaction and membrane disruption, and the interaction of small molecule compounds with amyloid proteins.[4,5] In the second-half of my presentation, structures of early intermediates of amyloid peptides, mechanisms of amyloid-induced membrane disruption, and amyloid inhibition by small molecule compounds will be discussed. Novel NMR and biophysical approaches to investigate amyloid formation and the role of cell membrane will also be presented. Particularly, our recent studies on the membrane interaction and cell toxicity of amyloid-beta, implicated in Alzheimer's Disease, and islet amyloid polypeptide (IAPP, or also known as amylin), implicated in Type-2 diabetes, will be discussed.

References
[1] Durr et al., BBA Biomembranes1768 (2007) 3235.
[2] Durr et al., Chem. Soc. Rev. 41 (2012) 608.
[3] Ravula et al., Angew. Chem.56 (2017) 11466-11470.
[4] Brender et al., Acc. Chem. Res. 116 (2012) 3650.
[5] Kotler et al., Chem.Soc.Rev. 43 (2014) 6692-6700.

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Lucie Khemtémourian
Sorbonne Université
Faculté des Sciences et Ingénierie
, UMR 7203 SU-ENS-CNRS
Laboratoire des Biomolécules