Magainin 2 and PGLa in Bacterial Membrane Mimics I:
Peptide-Peptide and Lipid-Peptide Interactions.

J 2019

Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions.

PACHLER, Michael, Ivo KABELKA, Marie-Sousai APPAVOU, Karl LOHNER, Robert VÁCHA et. al.

Basic information

Original name

Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions.

Authors

PACHLER, Michael, Ivo KABELKA (203 Czech Republic, belonging to the institution), Marie-Sousai APPAVOU, Karl LOHNER, Robert VÁCHA (203 Czech Republic, belonging to the institution) and Georg PABST

Edition

Biophysical Journal, New York, Cell Press, 2019, 0006-3495

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Full Text

Impact factor

Impact factor: 3.854

RIV identification code

RIV/00216224:14740/19:00107896

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.bpj.2019.10.022

UT WoS

000497815800009

Keywords in English

X-RAY-SCATTERING; ANTIMICROBIAL PEPTIDES; FORCE-FIELD; DYNAMICS; BILAYERS; MODEL; SIMULATIONS; VALIDATION; POTENTIALS; DERIVATION

Abstract

V originále

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.

Links

GA17-11571S, research and development project

Name: Amfifilní peptidy na fosfolipidových membránách

Investor: Czech Science Foundation

LM2015085, research and development project

Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

PACHLER, Michael, Ivo KABELKA, Marie-Sousai APPAVOU, Karl LOHNER, Robert VÁCHA and Georg PABST. Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions. Biophysical Journal. New York: Cell Press, 2019, vol. 117, No 10, p. 1858-1869. ISSN 0006-3495. Available from: https://dx.doi.org/10.1016/j.bpj.2019.10.022.

@article{1597058,
   author = {Pachler, Michael and Kabelka, Ivo and Appavou, MarieandSousai and Lohner, Karl and Vácha, Robert and Pabst, Georg},
   article_location = {New York},
   article_number = {10},
   doi = {http://dx.doi.org/10.1016/j.bpj.2019.10.022},
   keywords = {X-RAY-SCATTERING; ANTIMICROBIAL PEPTIDES; FORCE-FIELD; DYNAMICS; BILAYERS; MODEL; SIMULATIONS; VALIDATION; POTENTIALS; DERIVATION},
   language = {eng},
   issn = {0006-3495},
   journal = {Biophysical Journal},
   title = {Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions.},
   url = {https://www.sciencedirect.com/science/article/pii/S0006349519308707},
   volume = {117},
   year = {2019}
}

TY  - JOUR
ID  - 1597058
AU  - Pachler, Michael - Kabelka, Ivo - Appavou, Marie-Sousai - Lohner, Karl - Vácha, Robert - Pabst, Georg
PY  - 2019
TI  - Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions.
JF  - Biophysical Journal
VL  - 117
IS  - 10
SP  - 1858-1869
EP  - 1858-1869
PB  - Cell Press
SN  - 00063495
KW  - X-RAY-SCATTERING
KW  - ANTIMICROBIAL PEPTIDES
KW  - FORCE-FIELD
KW  - DYNAMICS
KW  - BILAYERS
KW  - MODEL
KW  - SIMULATIONS
KW  - VALIDATION
KW  - POTENTIALS
KW  - DERIVATION
UR  - https://www.sciencedirect.com/science/article/pii/S0006349519308707
L2  - https://www.sciencedirect.com/science/article/pii/S0006349519308707
N2  - 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.
ER  -

PACHLER, Michael, Ivo KABELKA, Marie-Sousai APPAVOU, Karl LOHNER, Robert VÁCHA and Georg PABST. Magainin 2 and PGLa in Bacterial Membrane Mimics I: Peptide-Peptide and Lipid-Peptide Interactions. \textit{Biophysical Journal}. New York: Cell Press, 2019, vol.~117, No~10, p.~1858-1869. ISSN~0006-3495. Available from: https://dx.doi.org/10.1016/j.bpj.2019.10.022.

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