Ambassadeur Tour des Sciences Chimiques

Il aura lieux le 12 novembre 2024 à 11h00 à l'IECB.

• Title: Probing Membrane-Assisted Protein-Protein Interactions by NMR

Molecular interactions at the cell membrane interface play vital roles on the pathomechanisms of various diseases including infection and aging related diseases. Therefore, high-resolution investigation of membrane-associated molecular events would be useful for biomedical applications. However, despite the recent developments in structural biology, probing dynamic protein-protein and protein-membrane interactions continues to pose tremendous challenges to most biophysical techniques. A major area of research in my group has been focused on the development of approaches to study the dynamic structural interactions between membrane bound proteins that are implicated in the pathology of many diseases. My lecture will focus on the approaches developed to overcome the major challenges related two such examples.

Our research has contributed towards the development of membrane mimetics (such as nanodiscs and bicelles) and NMR approaches to study the dynamic structural interactions between membrane bound proteins such as cytochromes (~16-kDa b5, ~57-kDa P450, ~80- kDa P450-reductase).1,2 Strategies to study the dynamic structures of these challenging systems and electron transfer mechanism related to cytochrome-P450’s enzymatic function will be presented in the first half of my talk.3,4 The development and applications of a variety of polymer-based nanodiscs will also be highlighted.

My research group has also been investigating the self-assembly process related to protein aggregation and phase separation.5-9 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. 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] Dürr et al., Chem. Rev. 112 (2012) 6054-6074.
[2] Dürr et al., BBA Biomembranes 1768 (2007) 3235-3259.
[3] Barnaba et al., Chem. Phys. Chem. 19 (2018) 2603-2613.
[4] Ravula et al., Angew. Chem. 56 (2021) 16885-16888.
[5] Brender et al., Acc. Chem. Res. 45 (2012) 454-462.
[6] Kotler et al., Chem. Soc. Rev. 43 (2014) 6692-6700.
[7] Milardi et al Chem. Rev. 121 (2021) 1845-1893.
[8] Ivanova et al Biophys. Chem. 269 (2021) 106507.
[9] Nguyen et al Chem. Rev. 121 (2021) 2545-2647.