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Exploration de la reconnaissance de la courbure membranaire par le motif ALPS

Abstract : Some biological processes such as vesicular transport are regulated by motifs that guide proteins to curved membranes. One of them is the ALPS (Amphipathic Lipid Packing Sensor) motif that recognizes packing defects induced by the convex curvature of the membrane. In this work, we combine molecular dynamics (MD) simulations and circular dichroism (CD) experiments to understand this phenomenon at the molecular level. MD simulations allowed us to characterize and quantify lipid packing defects. We show that packing defects caused by the membrane curvature are similar to those caused by the introduction of conical lipids in a flat bilayer composed of cylindrical lipids. By examining the interaction of the ALPS motif with a membrane containing such defects, we show that the early insertion of this motif on the membrane surface is driven by the inserton of its bulky hydrophobic residues in pre-existing defects. CD experiments and replica exchange MD simulations indicate that defects facilitate the ALPS folding into a partial alpha-helix. Finally, CD experiments allowed us to explore the thermodynamics of ALPS motif insertion as a function of lipid composition. Our work suggests that the peculiar amino-acid composition of the ALPS motif, as well as, its low helicity play a role in the recognition of packing defects, therefore curvature.
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Submitted on : Wednesday, January 22, 2014 - 12:18:40 AM
Last modification on : Wednesday, October 27, 2021 - 3:13:32 PM
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  • HAL Id : tel-00934412, version 1


Lydie Vamparys. Exploration de la reconnaissance de la courbure membranaire par le motif ALPS. Modélisation et simulation. Université Paris-Diderot - Paris VII, 2013. Français. ⟨NNT : ⟩. ⟨tel-00934412⟩



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