Maximally asymmetric transbilayer distribution of anionic lipids alters the structure and interaction with lipids of an amyloidogenic protein dimer bound to the membrane surface

Abstract

We used molecular dynamics simulations to explore the effects of asymmetric transbilayer distribution of anionic phosphatidylserine (PS) lipids on the structure of a protein on the membrane surface and subsequent protein–lipid interactions. Our simulation systems consisted of an amyloidogenic, beta-sheet rich dimeric protein (D42) absorbed to the phosphatidylcholine (PC) leaflet, or protein-contact PC leaflet, of two membrane systems: a single-component PC bilayer and double PC/PS bilayers. The latter comprised of a stable but asymmetric transbilayer distribution of PS in the presence of counterions, with a 1-component PC leaflet coupled to a 1-component PS leaflet in each bilayer. The maximally asymmetric PC/PS bilayer had a non-zero transmembrane potential (TMP) difference and higher lipid order packing, whereas the symmetric PC bilayer had a zero TMP difference and lower lipid order packing under physiologically relevant conditions. Analysis of the adsorbed protein structures revealed weaker protein binding, more folding in the N-terminal domain, more aggregation of the N- and C-terminal domains and larger tilt angle of D42 on the PC leaflet surface of the PC/PS bilayer versus the PC bilayer. Also, analysis of protein-induced membrane structural disruption revealed more localized bilayer thinning in the PC/PS versus PC bilayer. Although the electric field profile in the non-protein-contact PS leaflet of the PC/PS bilayer differed significantly from that in the non-protein-contact PC leaflet of the PC bilayer, no significant difference in the electric field profile in the protein-contact PC leaflet of either bilayer was evident. We speculate that lipid packing has a larger effect on the surface adsorbed protein structure than the electric field for a maximally asymmetric PC/PS bilayer. Our results support the mechanism that the higher lipid packing in a lipid leaflet promotes stronger protein–protein but weaker protein–lipid interactions for a dimeric protein on membrane surfaces.

Data supporting beta-amyloid dimer structural transitions and protein–lipid interactions on asymmetric lipid bilayer surfaces using MD simulations on experimentally derived NMR protein structures

“… This data article supports the research article entitled “Maximally Asymmetric Transbilayer Distribution of Anionic Lipids Alters the Structure and interaction with Lipids of an Amyloidogenic Protein Dimer Bound to the Membrane Surface” [1] . We describe supporting data on the binding kinetics, time evolution of secondary structure, and residue-contact maps of a surface-absorbed beta-amyloid dimer protein on different membrane surfaces.…”

“…The design of the initial structures ( Fig. 8 ) of the dimer protein and lipid bilayer systems is provided in Materials and Methods of the research article [1] . The data was created using in-house scripts (surround for annular and non-annular region identification, and a python script for sorting of DSSP output) [6] , [7] , g-tools (a suite of analysis programs available through the GROMACs MD engine [8] ) for secondary structure analysis, binding kinetics, and residue contact maps, and VMD [9] for visualization of structures.…”

“…These analysis methods used can be applied to any protein-lipid system, and can provide detailed information about protein structural changes over time when in contact with lipid membrane surfaces of differing composition. The design of the initial structures of the dimer protein and lipid bilayer systems can be found in the Material and Methods section of the research article [1] .…”

“…For clarity, only the phosphate atoms (silver) of the protein-contact PC leaflet and D42 (blue ribbon) are presented. A red arrow, starting from the last residue Ala-42 and ending at Lys-28 at the tip of the loop of the U-shaped chain A of D42, represents the membrane-orientation vector of the surface-contact region of D42 (see Materials and Methods of the research article [1] . The angle between the red arrow and the z -axis (as demonstrated in panel R), defined as the orientation angle, is given in red at each selected time as the protein establishes stable surface-contact with the PC leaflet during the protein surface-absorption on the lipid membrane.…”

Study of Irradiations to Enhance the Induces the Dissociation of Hydrogen Bonds between Peptide Chains and Transition from Helix Structure to Random Coil Structure Using ATRFTIR, Raman and 1HNMR Spectroscopies

“…The Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman and 1HNMR spectroscopies are used in order to observe the changes of molecular structures of these tissues. The effect of Near-Infrared (NIR) or IR-A, Short-Wavelength Infrared (SWIR) or IR-B, Mid-Wavelength Infrared (MWIR) or IR-C, Intermediate Infrared (IIR) or IR-C, Long-Wavelength Infrared (LWIR) or IR-C and Far-Infrared (FIR) lights was seen by noticing the changes of the Amide bands in absorption spectra of tissues, respectively [10][11][12][13][14][15][16][17][18][19]. (Figures 7-9).…”