Scaling and alpha-helix regulation of protein relaxation in a lipid bilayer.

Content Provider	Europe PMC
Author	Qiu, Liming Buie, Creighton Cheng, Kwan Hon Vaughn, Mark W.
Copyright Year	2014
Description	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.
Abstract	Protein conformation and orientation in the lipid membrane plays a key role in many cellularprocesses. Here we use molecular dynamics simulation to investigate the relaxation and C-terminusdiffusion of a model helical peptide: beta-amyloid (Aβ) in a lipid membrane. We observed that afterthe 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 anchoredto PC headgroups of the cytofacial lipid leaflet. In some cases, the membrane insertion domain ofthe Aβ was observed to partially unfold. Applying a sigmoidal fit to the process, we found that thecharacteristic velocity of the C-terminus, as it moved to its anchor site, scaled withθu−4/3, whereθu is the fraction of the original helix that was lostduring a helix to coil transition. Comparing this scaling with that of bead-spring models of polymerrelaxation 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 thepositive Lys28 side chain to the negative phosphate of PC or 3β oxygen of CHOL in the extracellularlipid leaflet and of the C-terminus to its anchor site in the cytofacial lipid leaflet.
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Page Count	9
ISSN	00219606
Volume Number	141
DOI	10.1063/1.4902229
PubMed Central reference number	PMC4265037
Issue Number	22
PubMed reference number	25494768
Journal	The Journal of Chemical Physics [J Chem Phys]
e-ISSN	10897690
Language	English
Publisher	American Institute of Physics
Publisher Date	2014-12-01
Access Restriction	Open
Rights License	0021-9606/2014/141(22)/225101/9/$30.00 Copyright © 2014 AIP Publishing LLC
Content Type	Text
Resource Type	Article
Subject	Physics and Astronomy Medicine Physical and Theoretical Chemistry