Buried lysine, but not arginine, titrates and alters transmembrane helix tilt

The ionization states of individual amino acid residues of membrane 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 wit...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-01, Vol.110 (5), p.1692-1695
Main Authors: Gleason, Nicholas J., Vostrikov, Vitaly V., Greathouse, Denise V., Koeppe, Roger E.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acids
Arginine - chemistry
Biochemistry
Biological Sciences
Cells
Electric potential
Hydrogen-Ion Concentration
Ionization
Lipid bilayers
Lipid Bilayers - chemistry
Lipids
Lysine - chemistry
Magnetic Resonance Spectroscopy
Membrane proteins
Membrane Proteins - chemistry
Membranes
Models, Molecular
Oligopeptides - chemistry
P branes
Protein Structure, Secondary
Proteins
Rotation
Titration
Titrimetry
Water - chemistry
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Summary:The ionization states of individual amino acid residues of membrane 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 pK ₐ 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 respect to the detailed lipid and protein environment.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1215400110