Date of Award
Spring 2024
Document Type
Thesis
Terms of Use
© 2024 Kyra Roepke. All rights reserved. This work is freely available courtesy of the author. It may only be used for non-commercial, educational, and research purposes. For all other uses, including reproduction and distribution, please contact the copyright holder.
Degree Name
Bachelor of Arts
Department
Chemistry & Biochemistry Department
First Advisor
Kathleen P. Howard
Abstract
Influenza A leads to annual epidemics that result in three-to-five million cases of severe illness each year and occasional devastating pandemics. Some current prevention and treatment methods target the M2 membrane protein on the surface of the virus. However, viral mutability and drug resistance require the targeting of more conserved parts of the protein.
The goal of this thesis was to investigate the secondary structure and dynamics of the M2 ectodomain (M2e), which is highly conserved across influenza viruses and across evolutionary time. The structure of M2e has previously been challenging to study because of its flexibility. In this study, I reconstituted full-length M2 protein into nanodiscs, which are model membrane bilayers surrounded by a structural membrane scaffold protein. To analyze the structure and dynamics of M2e, I used site-directed spin labeling electron paramagnetic resonance (SDSL-EPR).
I found that M2e is dynamic and flexible, with evidence of a turn between residues 14 and 21. Additionally, I found that residue 14 is membrane embedded, suggesting potential interactions between the M2e peptide and the lipid headgroups. These data are different from the trends found on the C-terminal tail of M2. In the presence of the antiviral drug rimantadine, M2e becomes less membrane embedded, indicating the presence of drug-induced conformational changes. In the presence of cholesterol, M2e similarly becomes less membrane embedded, which could provide evidence for interdomain coupling between M2e and the other domains of M2.
Recommended Citation
Roepke, Kyra , '24, "Thinking Outside the Membrane: Investigating the Structure of the Influenza A M2 Ectodomain" (2024). Senior Theses, Projects, and Awards. 905.
https://works.swarthmore.edu/theses/905