Related Articles(2)H-NMR and MD Simulations Reveal Membrane-Bound Conformation of Magainin 2 and Its Synergy with PGLa.
Biophys J. 2016 Nov 15;111(10):2149-2161
Authors: Strandberg E, Horn D, Reißer S, Zerweck J, Wadhwani P, Ulrich AS
Abstract
Magainin 2 (MAG2) and PGLa are two ?-helical antimicrobial peptides found in the skin of the African frog Xenopus laevis. They act by permeabilizing bacterial membranes and exhibit an exemplary synergism. Here, we determined the detailed molecular alignment and dynamical behavior of MAG2 in oriented lipid bilayers by using (2)H-NMR on Ala-d3-labeled peptides, which yielded orientation-dependent quadrupolar splittings of the labels. The amphiphilic MAG2 helix was found to lie flat on the membrane surface in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol (DMPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), as expected, with a tilt angle close to 90°. This orientation fits well with all-atom molecular-dynamics simulations of MAG2 performed in DMPC and DMPC/DMPG. In the presence of an equimolar amount of PGLa, the NMR analysis showed that MAG2 becames tilted at an angle of 120°, and its azimuthal rotation angle also changes. Since this interaction was found to occur in a concentration range where the peptides per se do not interact with their own type, we propose that MAG2 forms a stable heterodimer with PGLa. Given that the PGLa molecules in the complex are known to be flipped into a fully upright orientation, with a helix tilt close to 180°, they must make up the actual transmembrane pore. We thus suggest that the two negative charges on the C-terminus of the obliquely tilted MAG2 peptides neutralize some of the cationic groups on the upright PGLa helices. This would stabilize the assembly of PGLa into a toroidal pore with an overall reduced charge density, which could explain the mechanism of synergy.
[NMR paper] Molecular dynamics simulations on PGLa using NMR orientational constraints.
Molecular dynamics simulations on PGLa using NMR orientational constraints.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles Molecular dynamics simulations on PGLa using NMR orientational constraints.
J Biomol NMR. 2015 Nov;63(3):265-74
Authors: Sternberg U, Witter R
Abstract
NMR data obtained by solid state NMR from anisotropic samples are used as orientational constraints in molecular dynamics simulations for determining the...
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08-25-2016 06:10 PM
[NMR paper] Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs.
Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs.
Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs.
Nucleic Acids Res. 2016 May 18;
Authors: Krepl M, Cléry A, Blatter M, Allain FH, Sponer J
Abstract
RNA recognition motif (RRM) proteins represent an abundant class of proteins playing key roles in RNA biology. We present a joint atomistic molecular...
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Molecular dynamics simulations on PGLa using NMR orientational constraints
Molecular dynamics simulations on PGLa using NMR orientational constraints
Abstract
NMR data obtained by solid state NMR from anisotropic samples are used as orientational constraints in molecular dynamics simulations for determining the structure and dynamics of the PGLa peptide within a membrane environment. For the simulation the recently developed molecular dynamics with orientational constraints technique (MDOC) is used. This method introduces orientation dependent pseudo-forces into the COSMOS-NMR force field. Acting during a molecular dynamics...
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09-11-2015 06:48 AM
[NMR paper] Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR.
Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR.
Related Articles Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR.
J Biomol NMR. 2015 Jan 30;
Authors: Eddy MT, Su Y, Silvers R, Andreas L, Clark L, Wagner G, Pintacuda G, Emsley L, Griffin RG
Abstract
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Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR
Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR
Abstract
The human voltage dependent anion channel 1 (VDAC) is a 32Â*kDa β-barrel integral membrane protein that controls the transport of ions across the outer mitochondrial membrane. Despite the determination of VDAC solution and diffraction structures, a structural basis for the mechanism of its function is not yet fully understood. Biophysical studies suggest VDAC requires a lipid bilayer to achieve full function, motivating the need...
[NMR paper] The membrane-bound conformation of alpha-lactalbumin studied by NMR-monitored 1H exch
The membrane-bound conformation of alpha-lactalbumin studied by NMR-monitored 1H exchange.
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J Mol Biol. 2002 Aug 2;321(1):99-110
Authors: Halskau Ø, Frøystein NA, Muga A, Martínez A
The interaction of bovine alpha-lactalbumin (BLA) with negatively charged phospholipid bilayers was studied by NMR monitored 1H exchange to characterize the conformational transition that enables a water-soluble protein to associate with and partially insert...
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19F NMR analysis of the antimicrobial peptide PGLa bound to native cell membranes fro
19F NMR analysis of the antimicrobial peptide PGLa bound to native cell membranes from bacterial protoplasts and human erythrocytes.
Related Articles 19F NMR analysis of the antimicrobial peptide PGLa bound to native cell membranes from bacterial protoplasts and human erythrocytes.
J Am Chem Soc. 2010 Jul 7;132(26):8822-4
Authors: Ieronimo M, Afonin S, Koch K, Berditsch M, Wadhwani P, Ulrich AS
(19)F NMR is a unique tool to examine the structure of fluorine-labeled peptides in their native cellular environment, due to an exquisite sensitivity...
(2)H-NMR and MD Simulations Reveal Membrane-Bound Conformation of Magainin 2 and Its Synergy with PGLa.
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