Date of Award

Spring 2014

Document Type


Terms of Use

© 2014 Megan E. Thompson. 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


Chemistry & Biochemistry Department

First Advisor

Kathleen P. Howard


The M2 protein of the influenza A virus is a homotetrameric transmembrane proton channel implicated in several stages of the viral replication process. Each of its 97-residue monomers is known to include a transmembrane α-helix. but the structures of the N- and C-terminal domains have not yet been solved. A significant barrier to an atomic level understanding of the M2 protein is the difficulty associated with expression and purification of the full-length protein, which has primarily been studied in the form of truncated constructs covering the amphipathic helix and a short C-terminal segment. This C-terminal segment, which includes residues 46-62, has been shown for a truncated version of the protein to consist of an amphipathic helix lying on the membrane surface. Here, we present SDSL-EPR structural studies using full-length M2 constructs to examine sites 50-54 in the proposed amphipathic helix region of M2. Using power saturation data for the protein reconstituted into vesicles and CW spectra of M2FL in detergent micelles and in vesicles, we present a preliminary structure for this region in the full-length protein and compare these results to analogous data collected for truncated M2 constructs. These spectra suggest that this region forms an amphipathic helix in the full-length protein, as has been proposed for the truncated form, with slightly reduced mobility and possibly a more deeply membrane-buried position relative to the truncation. We also find that mobility across this region is severely constrained when either the full- length or the truncated protein is solubilized into neutral octyl glucoside micelles, though the truncated form is known to remain highly mobile in micelles of zwitterionic detergents. From these results, we suggest that the chemical nature of amphiphile headgroups dictates association of the C-terminal domain with the membrane mimic surface.

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