Flanking aromatic residue competition influences transmembrane peptide helix dynamics

by McKay, M. J.; Greathouse, D. V.; Koeppe, R. E.

To address biophysical principles and lipid interactions that underlie the properties of membrane proteins, modifications that vary the neighbors of tryptophan residues in the highly dynamic transmembrane helix of GW(4,20)ALP23 (acetyl-GGAW(4)A(LA)(6)LAW(20)AGA-amide) were examined using deuterium NMR spectroscopy. It was found that L(5,19)GW(4,20)ALP23, a sequence isomer of the low to moderately dynamic GW(5,19)ALP23, remains highly dynamic. By contrast, a removal of W4 to produce F(4,5)GW(20)ALP23 restores a low level of dynamic averaging, similar to that of the F(4,5)GW(19)ALP23 helix. Interestingly, a high level of dynamic averaging requires the presence of both tryptophan residues W4 and W20, on opposite faces of the helix, and does not depend on whether residue 5 is Leu or Ala. Aspects of helix unwinding and potential oligomerization are discussed with respect to helix dynamic averaging and the locations of particular residues at a phosphocholine membrane interface.

Journal
FEBS Letters
Volume
594
Issue
24
Year
2020
Start Page
4280-4291
URL
https://dx.doi.org/10.1002/1873-3468.13926
ISBN/ISSN
1873-3468; 0014-5793
DOI
10.1002/1873-3468.13926