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Accommodation of a Central Arginine in a Transmembrane Peptide by Changing the Placement of Anchor Residues

Author:
Vostrikov, Vitaly V., Hall, Benjamin A., Sansom, Mark S. P., Koeppe, Roger E.
Source:
The Journal of physical chemistry 2012 v.116 no.43 pp. 12980-12990
ISSN:
1520-5207
Subject:
arginine, deuterium, lipid bilayers, lipids, molecular dynamics, nuclear magnetic resonance spectroscopy, peptides, stable isotopes, transmembrane proteins
Abstract:
Both Trp and Arg in transmembrane protein domains make important interactions with lipids at the membrane/water interface, but at different depths. Derivatives of the designed peptide GWALP23, acetyl-GGALW⁵LALALALALALALW¹⁹LAGA-amide, with single Trp anchors, have proven useful for characterizing such interactions. Indeed, previous work revealed quite different effects emanating from Arg substitutions at positions 12 and 14 within GWALP23, with the R12 peptide exhibiting multiple positions and orientations with respect to DOPC bilayer membranes (Vostrikov et al. J. Am. Chem. Soc. 2010, 132, 5803–5811). To gain further understanding of the multistate behavior, we moved the Trp “anchor” residues to more outer positions 3 and 21 in GWALP23 itself, and in the R12 and R14 derivatives. The locations and orientations of the peptides with respect to lipid bilayer membranes of differing thickness were investigated by means of solid-state ²H NMR spectroscopy, using labeled alanines, and coarse-grained molecular dynamics simulations. Interestingly, relatively intense and narrow ²H resonances from selected backbone Cα deuterons were observed over quite narrow ranges of frequency and sample orientation. The backbone resonances reflect dynamic complexities and at the same time provide important contributions for the analysis of peptide transmembrane orientation. With the Trp³,²¹ anchors relatively far from the peptide and bilayer center, the results indicate significantly large apparent tilt angles, for example, close to 30° for the new R12 and R14 peptides with respect to the bilayer normal of DLPC membranes. The R12 side chain indeed is “rescued” to a stable position, where it is accommodated within the transmembrane helix, when the Trp anchors are moved outward and to another face of the helix. At the same time, the R14 side chain of transmembrane GW³,²¹ALP23 also retains a stable favored position.
Agid:
5582784