Journal
STRUCTURE
Volume 16, Issue 7, Pages 1067-1076Publisher
CELL PRESS
DOI: 10.1016/j.str.2008.04.011
Keywords
-
Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NIAID NIH HHS [AI-31882, R01 AI031882-10, AI-20201, R01 AI031882] Funding Source: Medline
- NIGMS NIH HHS [R01 GM056423-12, GM56423, T32 GM008275, R01 GM056423] Funding Source: Medline
Ask authors/readers for more resources
We explore the interplay between amino acid sequence, thermodynamic stability, and functional fitness in the M2 proton channel of influenza A virus. Electrophysiological measurements show that drug-resistant mutations have minimal effects on M2's specific activity, and suggest that resistance is achieved by altering a binding site within the pore rather than a less direct allosteric mechanism. In parallel, we measure the effects of these mutations on the free energy of assembling the homotetrameric transmembrane pore from monomeric helices in micelles and bilayers. Although there is no simple correlation between the evolutionary fitness of the mutants and their stability, all variants formed more stable tetramers in bilayers, and the least-fit mutants showed the smallest increase in stability upon moving from a micelle to a bilayer environment. We speculate that the folding landscape of a micelle, is rougher than that of a bilayer, and more accommodating of conformational variations in nonoptimized mutants.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available