TY - JOUR
T1 - Maximally asymmetric transbilayer distribution of anionic lipids alters the structure and interaction with lipids of an amyloidogenic protein dimer bound to the membrane surface
AU - Cheng, Sara Y.
AU - Chou, George
AU - Buie, Creighton
AU - Vaughn, Mark W.
AU - Compton, Campbell
AU - Cheng, Kwan H.
N1 - Funding Information:
This work was supported by the Robert A. Welch Research Foundation grant ( D-1158 ), NIH grant ( GM090897-02 ), National Science Foundation ( ACI 1531594 ), Williams Endowment fund of Trinity University , Texas Advanced Computing Center (TACC) for the use of Lonestar Cluster under the project ( G-803132 ) “Protein Unfolding in Lipid Membranes”, and Texas Tech University High Performance Computing Center (TTU-HPCC) for supporting in computing. The authors would like to acknowledge the valuable help of Dr. Andrey A. Gurtovenko of the Institute of Macromolecular Compounds, Russian Academy of Sciences for allowing us to use the published asymmetric PC/PS bilayer system and valuable advice on the simulation details of the PC/PS bilayer system.
Publisher Copyright:
© 2016 Elsevier Ireland Ltd. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Asymmetric lipid membrane
KW - Beta-amyloid
KW - Molecular dynamics simulations
KW - Protein aggregation
KW - Protein structures on surfaces
KW - Protein-lipid interactions
UR - http://www.scopus.com/inward/record.url?scp=84958770650&partnerID=8YFLogxK
U2 - 10.1016/j.chemphyslip.2016.01.002
DO - 10.1016/j.chemphyslip.2016.01.002
M3 - Article
C2 - 26827904
AN - SCOPUS:84958770650
SN - 0009-3084
VL - 196
SP - 33
EP - 51
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
ER -