Binding to the lipid monolayer induces conformational transition in Aβ monomer.
Using implicit solvent atomistic model and replica exchange molecular dynamics, we study binding of Aβ monomer to zwitterionic dimyristoylphosphatidylcholine (DMPC) lipid monolayer. Our results suggest that Aβ binding to the monolayer is governed primarily by positively charged and aromatic amino acids. Lysine residues tend to interact with surface choline and phosphorous lipid groups, whereas aromatic amino acids penetrate deeper into the monolayer, reaching its hydrophobic core. We show that binding to the DMPC monolayer causes a dramatic conformational transition in Aβ monomer, resulting in chain extension, loss of intrapeptide interactions, and formation of β-structure. This conformational transition is far more significant than that occurring during the initial stages of aggregation in water. We also found that Aβ binding perturbs surface ordering of lipids interacting with Aβ.
School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
Seongwon
S
Kim
Dmitri K
DK
Klimov
D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008239:Lysine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013499:Surface Properties; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D024322:Amino Acids, Aromatic; D016229:Amyloid beta-Peptides; D014867:Water; D008239:Lysine; D004134:Dimyristoylphosphatidylcholine