Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biophys J
2012 Aug 08;1033:472-482. doi: 10.1016/j.bpj.2012.06.040.
Show Gene links
Show Anatomy links
Reorientation and dimerization of the membrane-bound antimicrobial peptide PGLa from microsecond all-atom MD simulations.
Ulmschneider JP
,
Smith JC
,
Ulmschneider MB
,
Ulrich AS
,
Strandberg E
.
???displayArticle.abstract???
The membrane-active antimicrobial peptide PGLa from Xenopus laevis is known from solid-state (2)H-, (15)N-, and (19)F-NMR spectroscopy to occupy two distinct α-helical surface adsorbed states in membranes: a surface-bound S-state with a tilt angle of ~95° at low peptide/lipid molar ratio (P/L = 1:200), and an obliquely tilted T-state with a tilt angle of 127° at higher peptide concentration (P/L = 1:50). Using a rapid molecular-dynamics insertion protocol in combination with microsecond-scale simulation, we have characterized the structure of both states in detail. As expected, the amphiphilic peptide resides horizontally on the membrane surface in a monomeric form at a low P/L, whereas the T-state is seen in the simulations to be a symmetric antiparallel dimer, with close contacts between small glycine and alanine residues at the interface. The computed tilt angles and azimuthal rotations, as well as the quadrupolar splittings predicted from the simulations agree with the experimental NMR data. The simulations reveal many structural details previously inaccessible, such as the immersion depth of the peptide in the membrane and the packing of the dimerization interface. The study highlights the ability and limitations of current state-of-the-art multimicrosecond all-atom simulations of membrane-active peptides to complement experimental data from solid-state NMR.
Afonin,
Evaluating the amino acid CF3-bicyclopentylglycine as a new label for solid-state 19 F-NMR structure analysis of membrane-bound peptides.
2007, Pubmed
Afonin,
Evaluating the amino acid CF3-bicyclopentylglycine as a new label for solid-state 19 F-NMR structure analysis of membrane-bound peptides.
2007,
Pubmed
Afonin,
Temperature-dependent transmembrane insertion of the amphiphilic peptide PGLa in lipid bilayers observed by solid state 19F NMR spectroscopy.
2008,
Pubmed
Andreu,
Solid-phase synthesis of PYLa and isolation of its natural counterpart, PGLa [PYLa-(4-24)] from skin secretion of Xenopus laevis.
1985,
Pubmed
,
Xenbase
Bechinger,
Orientations of amphipathic helical peptides in membrane bilayers determined by solid-state NMR spectroscopy.
1991,
Pubmed
,
Xenbase
Bechinger,
Orientations of helical peptides in membrane bilayers by solid state NMR spectroscopy.
1996,
Pubmed
,
Xenbase
Bechinger,
Structure and dynamics of the antibiotic peptide PGLa in membranes by solution and solid-state nuclear magnetic resonance spectroscopy.
1998,
Pubmed
Bürck,
Conformation and membrane orientation of amphiphilic helical peptides by oriented circular dichroism.
2008,
Pubmed
Bussi,
Canonical sampling through velocity rescaling.
2007,
Pubmed
Chinchar,
Inactivation of viruses infecting ectothermic animals by amphibian and piscine antimicrobial peptides.
2004,
Pubmed
Epand,
Diversity of antimicrobial peptides and their mechanisms of action.
1999,
Pubmed
Glaser,
Concentration-dependent realignment of the antimicrobial peptide PGLa in lipid membranes observed by solid-state 19F-NMR.
2005,
Pubmed
Glaser,
Orientation of the antimicrobial peptide PGLa in lipid membranes determined from 19F-NMR dipolar couplings of 4-CF3-phenylglycine labels.
2004,
Pubmed
Gurtovenko,
Defect-mediated trafficking across cell membranes: insights from in silico modeling.
2010,
Pubmed
Hara,
Heterodimer formation between the antimicrobial peptides magainin 2 and PGLa in lipid bilayers: a cross-linking study.
2001,
Pubmed
,
Xenbase
Helmerhorst,
A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides.
1999,
Pubmed
,
Xenbase
Hoffmann,
A novel peptide designated PYLa and its precursor as predicted from cloned mRNA of Xenopus laevis skin.
1983,
Pubmed
,
Xenbase
Holt,
Orientation and dynamics of transmembrane peptides: the power of simple models.
2010,
Pubmed
Hoskin,
Studies on anticancer activities of antimicrobial peptides.
2008,
Pubmed
Hristova,
Structure, location, and lipid perturbations of melittin at the membrane interface.
2001,
Pubmed
Janosi,
Lipid-modulated sequence-specific association of glycophorin A in membranes.
2010,
Pubmed
Jean-François,
Pore formation induced by an antimicrobial peptide: electrostatic effects.
2008,
Pubmed
Kalli,
A helix heterodimer in a lipid bilayer: prediction of the structure of an integrin transmembrane domain via multiscale simulations.
2011,
Pubmed
Klauda,
Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.
2010,
Pubmed
Konovalov,
Lipid discrimination in phospholipid monolayers by the antimicrobial frog skin peptide PGLa. A synchrotron X-ray grazing incidence and reflectivity study.
2002,
Pubmed
,
Xenbase
Leontiadou,
Antimicrobial peptides in action.
2006,
Pubmed
MacKerell,
All-atom empirical potential for molecular modeling and dynamics studies of proteins.
1998,
Pubmed
Maloy,
Structure-activity studies on magainins and other host defense peptides.
1995,
Pubmed
Matsuzaki,
Mechanism of synergism between antimicrobial peptides magainin 2 and PGLa.
1998,
Pubmed
,
Xenbase
Matsuzaki,
Orientational and aggregational states of magainin 2 in phospholipid bilayers.
1994,
Pubmed
,
Xenbase
Ozdirekcan,
On the orientation of a designed transmembrane peptide: toward the right tilt angle?
2007,
Pubmed
Psachoulia,
Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization.
2008,
Pubmed
Psachoulia,
Molecular dynamics simulations of the dimerization of transmembrane alpha-helices.
2010,
Pubmed
Rathinakumar,
Biomolecular engineering by combinatorial design and high-throughput screening: small, soluble peptides that permeabilize membranes.
2008,
Pubmed
Richter,
Biosynthesis of peptides in the skin of Xenopus laevis: isolation of novel peptides predicted from the sequence of cloned cDNAs.
1985,
Pubmed
,
Xenbase
Salnikov,
Lipid-controlled peptide topology and interactions in bilayers: structural insights into the synergistic enhancement of the antimicrobial activities of PGLa and magainin 2.
2011,
Pubmed
Sengupta,
Toroidal pores formed by antimicrobial peptides show significant disorder.
2008,
Pubmed
Sengupta,
Lipid-mediated interactions tune the association of glycophorin A helix and its disruptive mutants in membranes.
2010,
Pubmed
Shai,
From "carpet" mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides.
2001,
Pubmed
Soravia,
Antimicrobial properties of peptides from Xenopus granular gland secretions.
1988,
Pubmed
,
Xenbase
Strandberg,
Synergistic transmembrane insertion of the heterodimeric PGLa/magainin 2 complex studied by solid-state NMR.
2009,
Pubmed
,
Xenbase
Strandberg,
Solid-state NMR analysis of the PGLa peptide orientation in DMPC bilayers: structural fidelity of 2H-labels versus high sensitivity of 19F-NMR.
2006,
Pubmed
Strandberg,
Lipid shape is a key factor for membrane interactions of amphipathic helical peptides.
2012,
Pubmed
Strandberg,
Solid-state NMR analysis comparing the designer-made antibiotic MSI-103 with its parent peptide PGLa in lipid bilayers.
2008,
Pubmed
,
Xenbase
Toke,
Structure of (KIAGKIA)3 aggregates in phospholipid bilayers by solid-state NMR.
2004,
Pubmed
Tremouilhac,
Synergistic transmembrane alignment of the antimicrobial heterodimer PGLa/magainin.
2006,
Pubmed
,
Xenbase
Tremouilhac,
Conditions affecting the re-alignment of the antimicrobial peptide PGLa in membranes as monitored by solid state 2H-NMR.
2006,
Pubmed
Ulmschneider,
In silico partitioning and transmembrane insertion of hydrophobic peptides under equilibrium conditions.
2011,
Pubmed
Ulmschneider,
Mechanism and kinetics of peptide partitioning into membranes from all-atom simulations of thermostable peptides.
2010,
Pubmed
Ulmschneider,
Peptide Partitioning and Folding into Lipid Bilayers.
2009,
Pubmed
Ulmschneider,
United Atom Lipid Parameters for Combination with the Optimized Potentials for Liquid Simulations All-Atom Force Field.
2009,
Pubmed
Ulmschneider,
Folding Peptides into Lipid Bilayer Membranes.
2008,
Pubmed
van 't Hof,
Antimicrobial peptides: properties and applicability.
2001,
Pubmed
Wadhwani,
Using a sterically restrictive amino acid as a 19F NMR label to monitor and to control peptide aggregation in membranes.
2008,
Pubmed
Wakamatsu,
Dimer structure of magainin 2 bound to phospholipid vesicles.
2002,
Pubmed
,
Xenbase
Wieprecht,
Membrane binding and pore formation of the antibacterial peptide PGLa: thermodynamic and mechanistic aspects.
2000,
Pubmed
,
Xenbase
