title: Orientation and dynamics of peptides in membranes calculated from 2H-NMR data.
abstract: Solid-state (2)H-NMR is routinely used to determine the alignment of membrane-bound peptides. Here we demonstrate that it can also provide a quantitative measure of the fluctuations around the distinct molecular axes. Using several dynamic models with increasing complexity, we reanalyzed published (2)H-NMR data on two representative alpha-helical peptides: 1), the amphiphilic antimicrobial peptide PGLa, which permeabilizes membranes by going from a monomeric surface-bound to a dimeric tilted state and finally inserting as an oligomeric pore; and 2), the hydrophobic WALP23, which is a typical transmembrane segment, although previous analysis had yielded helix tilt angles much smaller than expected from hydrophobic mismatch and molecular dynamics simulations. Their (2)H-NMR data were deconvoluted in terms of the two main helix orientation angles (representing the time-averaged peptide tilt and azimuthal rotation), as well as the amplitudes of fluctuation about the corresponding molecular axes (providing the dynamic picture). The mobility of PGLa is found to be moderate and to correlate well with the respective oligomeric states. WALP23 fluctuates more vigorously, now in better agreement with the molecular dynamics simulations and mismatch predictions. The analysis demonstrates that when (2)H-NMR data are fitted to extract peptide orientation angles, an explicit representation of the peptide rigid-body angular fluctuations should be included.
authors.affiliation: Karlsruhe Institute of Technology, Institute for Biological Interfaces, Forschungszentrum Karlsruhe, 76021 Karlsruhe, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Strandberg
authors.forename: Santi
authors.initials: S
authors.lastname: Esteban-Martín
authors.forename: Jesús
authors.initials: J
authors.lastname: Salgado
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C045866:peptide-Gly-Leu-amide