title: Scaling and alpha-helix regulation of protein relaxation in a lipid bilayer.
abstract: Protein conformation and orientation in the lipid membrane plays a key role in many cellular processes. Here we use molecular dynamics simulation to investigate the relaxation and C-terminus diffusion of a model helical peptide: beta-amyloid (Aβ) in a lipid membrane. We observed that after the helical peptide was initially half-embedded in the extracelluar leaflet of phosphatidylcholine (PC) or PC/cholesterol (PC/CHOL) membrane, the C-terminus diffused across the membrane and anchored to PC headgroups of the cytofacial lipid leaflet. In some cases, the membrane insertion domain of the Aβ was observed to partially unfold. Applying a sigmoidal fit to the process, we found that the characteristic velocity of the C-terminus, as it moved to its anchor site, scaled with θu (-4/3), where θu is the fraction of the original helix that was lost during a helix to coil transition. Comparing this scaling with that of bead-spring models of polymer relaxation suggests that the C-terminus velocity is highly regulated by the peptide helical content, but that it is independent of the amino acid type. The Aβ was stabilized by the attachment of the positive Lys28 side chain to the negative phosphate of PC or 3β oxygen of CHOL in the extracellular lipid leaflet and of the C-terminus to its anchor site in the cytofacial lipid leaflet.
authors.affiliation: Department of Physics, Texas Tech University, Lubbock, Texas 79409, USA.
authors.forename: Liming
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Chemical Engineering, Texas Tech University, Lubbock, Texas 79409, USA.
authors.forename: Creighton
authors.initials: C
authors.lastname: Buie
authors.affiliation: Department of Physics, Texas Tech University, Lubbock, Texas 79409, USA.
authors.forename: Kwan Hon
authors.initials: KH
authors.lastname: Cheng
authors.affiliation: Department of Chemical Engineering, Texas Tech University, Lubbock, Texas 79409, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Vaughn
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D004058:Diffusion; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers