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@ARTICLE{Pachler:867574,
author = {Pachler, Michael and Kabelka, Ivo and Appavou, Marie-Sousai
and Lohner, Karl and Vácha, Robert and Pabst, Georg},
title = {{M}againin 2 and {PGL}a in {B}acterial {M}embrane {M}imics
{I}: {P}eptide-{P}eptide and {L}ipid-{P}eptide
{I}nteractions},
journal = {Biophysical journal},
volume = {117},
number = {10},
issn = {0006-3495},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {FZJ-2019-06197},
pages = {1858 - 1869},
year = {2019},
abstract = {We addressed the onset of synergistic activity of the two
well-studied antimicrobial peptides magainin 2 (MG2a) and
PGLa using lipid-only mimics of Gram-negative cytoplasmic
membranes. Specifically, we coupled a joint analysis of
small-angle x-ray and neutron scattering experiments on
fully hydrated lipid vesicles in the presence of MG2a and
L18W-PGLa to all-atom and coarse-grained molecular dynamics
simulations. In agreement with previous studies, both
peptides, as well as their equimolar mixture, were found to
remain upon adsorption in a surface-aligned topology and to
induce significant membrane perturbation, as evidenced by
membrane thinning and hydrocarbon order parameter changes in
the vicinity of the inserted peptide. These effects were
particularly pronounced for the so-called synergistic
mixture of 1:1 (mol/mol) L18W-PGLa/MG2a and cannot be
accounted for by a linear combination of the membrane
perturbations of two peptides individually. Our data are
consistent with the formation of parallel heterodimers at
concentrations below a synergistic increase of dye leakage
from vesicles. Our simulations further show that the
heterodimers interact via salt bridges and hydrophobic
forces, which apparently makes them more stable than
putatively formed antiparallel L18W-PGLa and MG2a
homodimers. Moreover, dimerization of L18W-PGLa and MG2a
leads to a relocation of the peptides within the lipid
headgroup region as compared to the individual peptides. The
early onset of dimerization of L18W-PGLa and MG2a at low
peptide concentrations consequently appears to be key to
their synergistic dye-releasing activity from lipid vesicles
at high concentrations},
cin = {JCNS-FRM-II / JCNS-1 / MLZ},
ddc = {570},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)JCNS-1-20110106 / I:(DE-588b)4597118-3},
pnm = {6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)
/ 6G15 - FRM II / MLZ (POF3-6G15)},
pid = {G:(DE-HGF)POF3-6G4 / G:(DE-HGF)POF3-6G15},
experiment = {EXP:(DE-MLZ)KWS1-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31703802},
UT = {WOS:000497815800009},
doi = {10.1016/j.bpj.2019.10.022},
url = {https://juser.fz-juelich.de/record/867574},
}