Flanking aromatic residue competition influences transmembrane peptide helix dynamics

Abstract

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-GGAW⁴ A(LA)₆ LAW²⁰ 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 GW²⁰ ALP23 restores a low level of dynamic averaging, similar to that of the F^4,5 GW¹⁹ 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.

Keywords: interfacial amino acid side chains; leucine; solid-state deuterium NMR; transmembrane helix dynamics; tryptophan.