The ionization statesofindividual amino acid residues ofmembrane proteins are difficult to decipher or assign directly in the lipid-bilayer membrane environment. We address this issue for lysines and arginines in designed transmembrane helices. For lysines (but not arginines) at two locations within dioleoyl-phosphatidylcholine bilayer membranes, we measure pKa values below 7.0. We find that buried charged lysine, in fashion similar to arginine, will modulate helix orientation to maximize its own access to the aqueous interface or, if occluded by aromatic rings, may cause a transmembrane helix to exit the lipid bilayer. Interestingly, the influence of neutral lysine (vis-à-vis leucine) upon helix orientation also depends upon its aqueous access. Our results suggest that changes in the ionization states of particular residues will regulate membrane protein function and furthermore illustrate the subtle complexity of ionization behavior with respecttothe detailed lipid and protein environment.
|Original language||English (US)|
|Number of pages||4|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Jan 29 2013|
- Lysine titration
- Solid-state deuterium NMR