Thema der Dissertation:
Investigating the Channel Opening Mechanism of the Influenza A M2 Protein by Combining Vibrational and Computational Spectroscopy
Investigating the Channel Opening Mechanism of the Influenza A M2 Protein by Combining Vibrational and Computational Spectroscopy
Abstract: Influenza A virus causes seasonal epidemics that result in thousands of deaths worldwide each year, making research on viral proteins such as the proton channel matrix protein 2 (M2) essential for antiviral drug development and for understanding the molecular mechanisms of structurally related ion channels in other human-pathogenic viruses. The thesis investigates the proton channel mechanism of M2, by combining surface-enhanced infrared absorption (SEIRA) spectroscopy and density functional theory (DFT) calculations. With this approach the opening motion of the channel was quantified and the role of carboxylate protonation was assessed, revealing mutation-induced structural changes and their effect on the opening mechanism. It was revealed that M2 opens by 17 ± 2° with a three-step transition in a pH range of pH 8 to around pH 4. Interestingly, carboxylate protonation events were found to contribute to these transitions. Mutations of Asp24 and also Asp44 led to changes in both structure and opening mechanism of the protein, where pKA values of the transition were either shifted or completely absent in the variants. This indicates that the role of these aspartates in the mechanism has been underestimated in previous studies. Understanding this mechanism and establishing methods to study it may pave the way for future medical research on influenza A and other human-pathogenic viruses with similar proton channels.
Zeit & Ort
14.08.2026 | 14:00
Hörsaal B (0.1.01)
(Fachbereich Physik, Arnimallee 14, 14195 Berlin)