Search results for "Hydrophobic mismatch"

The Role of Hydrophobic Mismatch on Transmembrane Helix Dimerization in Living Cells

2019

Hydrophobic mismatch of mobile transmembrane helices: Merging theory and experiments

2012

Abstract Hydrophobic mismatch still represents a puzzle for transmembrane peptides, despite the apparent simplicity of this concept and its demonstrated validity in natural membranes. Using a wealth of available experimental 2 H NMR data, we provide here a comprehensive explanation of the orientation and dynamics of model peptides in lipid bilayers, which shows how they can adapt to membranes of different thickness. The orientational adjustment of transmembrane α-helices can be understood as the result of a competition between the thermodynamically unfavorable lipid repacking associated with peptide tilting and the optimization of peptide/membrane hydrophobic coupling. In the positive misma…

The role of hydrophobic matching on transmembrane helix packing in cells

2017

Folding and packing of membrane proteins are highly influenced by the lipidic component of the membrane. Here, we explore how the hydrophobic mismatch (the difference between the hydrophobic span of a transmembrane protein region and the hydrophobic thickness of the lipid membrane around the protein) influences transmembrane helix packing in a cellular environment. Using a ToxRED assay in Escherichia coli and a Bimolecular Fluorescent Complementation approach in human-derived cells complemented by atomistic molecular dynamics simulations we analyzed the dimerization of Glycophorin A derived transmembrane segments. We concluded that, biological membranes can accommodate transmembrane homo-di…

Detergent Properties Influence the Stability of the Glycophorin A Transmembrane Helix Dimer in Lysophosphatidylcholine Micelles

2012

AbstractDetergents might affect membrane protein structures by promoting intramolecular interactions that are different from those found in native membrane bilayers, and fine-tuning detergent properties can be crucial for obtaining structural information of intact and functional transmembrane proteins. To systematically investigate the influence of the detergent concentration and acyl-chain length on the stability of a transmembrane protein structure, the stability of the human glycophorin A transmembrane helix dimer has been analyzed in lyso-phosphatidylcholine micelles of different acyl-chain length. While our results indicate that the transmembrane protein is destabilized in detergents w…

Experiments Meet Hydrophobic Mismatch: A Re-evaluation Of The Orientation Of Model Transmembrane Peptides From Solid-State NMR

2009

The basic physical rules underlying the organization of biological membranes can be gathered under the simple, but powerful, concept of hydrophobic mismatch. For example, the mutual adjustment of the lipid and protein hydrophobic lengths can be related with the existence of lipid rafts and explain discrete secretory pathways in the Golgi apparatus. The orientation of membrane protein fragments is predicted to follow the same hydrophobic mismatch principles, as illustrated by some experiments and molecular dynamics simulations. However, this appears to be challenged by results of solid-state 2H NMR experiments on model transmembrane peptides, displaying tilt angle values unexpectedly small a…

Membrane-mediated Protein-protein Interaction: A Monte Carlo Study

2012

We investigate membrane-mediated interactions between transmembrane proteins using coarse-grained models. We compare the effective potential of mean force (PMF) between two proteins, which are always aligned parallel to the z-axis of the simulation box, with those PMFs obtained for proteins with fluctuating orientations. The PMFs are dominated by an oscillatory packing-driven contribution and a smooth attractive hydrophobic mismatch contribution, which vanishes if the hydrophobic length of the protein matches the thickness of the membrane. If protein orientations are allowed to fluctuate, the oscillations are greatly reduced compared to proteins with fixed orientation. Furthermore, the hydr…

Influence of hydrophobic matching on association of model transmembrane fragments containing a minimised glycophorin A dimerisation motif

2005

AbstractThe principles that govern the folding and packing of membrane proteins are still not completely understood. In the present work, we have revisited the glycophorin A (GpA) dimerisation motif that mediates transmembrane (TM) helix association, one of the best-suited models of membrane protein oligomerisation. By using artificial polyleucine TM segments we have demonstrated in this study that a pattern of only five amino acids (GVxxGVxxT) promotes specific dimerisation. Further, we have used this minimised GpA motif to assess the influence of hydrophobic matching on the TM helix packing process in detergent micelles and found that this factor modulates helix–helix association and/or d…

Structures of single, double and triple layers of lipids adsorbed on graphene: Insights from all-atom molecular dynamics simulations

2017

Abstract Non-covalent functionalization of graphene with phospholipids is a promising technique for biosensing applications and intracellular delivery of analytical probes and drugs. However, molecular details of the self-assembly of lipids on graphene surface is still poorly understood and hard to control. There is a clear lack of understanding of why various kinds of lipid aggregates can form on graphene. In the current work, we address this question by investigating equilibrium and dynamical properties of lipid layers adsorbed on graphene in water environment and in vacuum using all-atom Molecular Dynamics simulations. It is shown that a variety of lipid aggregates can form on top of gra…

Orientation and Dynamics of Peptides in Membranes Calculated from 2H-NMR Data

2009

Solid-state (2)H-NMR is routinely used to determine the alignment of membrane-bound peptides. Here we demonstrate that it can also provide a quantitative measure of the fluctuations around the distinct molecular axes. Using several dynamic models with increasing complexity, we reanalyzed published (2)H-NMR data on two representative alpha-helical peptides: 1), the amphiphilic antimicrobial peptide PGLa, which permeabilizes membranes by going from a monomeric surface-bound to a dimeric tilted state and finally inserting as an oligomeric pore; and 2), the hydrophobic WALP23, which is a typical transmembrane segment, although previous analysis had yielded helix tilt angles much smaller than ex…

Interactions of membranes with coarse-grain proteins: a comparison

2012

We study the interactions between lipid bilayers and rigid transmembrane proteins by Monte Carlo simulations of generic coarse-grain models. Different popular protein models are considered and compared with each other, and key parameters such as the hydrophobicity and the hydrophobic mismatch are varied systematically. Furthermore, the properties of the membrane are manipulated by applying different tensions. The response of the membrane to the insertion of single proteins is found to be mostly generic and independent of the choice of the protein model. Likewise, the orientational distributions of single proteins depend mainly on the hydrophobic mismatch and the hydrophobicity of the protei…