Quantitative modeling of membrane deformations by multihelical membrane proteins: Application to G-protein coupled receptors Academic Article uri icon

Overview

MeSH Major

  • Lipid Bilayers
  • Models, Molecular
  • Receptor, Serotonin, 5-HT2A
  • Rhodopsin

abstract

  • The interpretation of experimental observations of the dependence of membrane protein function on the properties of the lipid membrane environment calls for a consideration of the energy cost of protein-bilayer interactions, including the protein-bilayer hydrophobic mismatch. We present a novel (to our knowledge) multiscale computational approach for quantifying the hydrophobic mismatch-driven remodeling of membrane bilayers by multihelical membrane proteins. The method accounts for both the membrane remodeling energy and the energy contribution from any partial (incomplete) alleviation of the hydrophobic mismatch by membrane remodeling. Overcoming previous limitations, it allows for radially asymmetric bilayer deformations produced by multihelical proteins, and takes into account the irregular membrane-protein boundaries. The approach is illustrated by application to two G-protein coupled receptors: rhodopsin in bilayers of different thickness, and the serotonin 5-HT(2A) receptor bound to pharmacologically different ligands. Analysis of the results identifies the residual exposure that is not alleviated by bilayer adaptation, and its quantification at specific transmembrane segments is shown to predict favorable contact interfaces in oligomeric arrays. In addition, our results suggest how distinct ligand-induced conformations of G-protein coupled receptors may elicit different functional responses through differential effects on the membrane environment.

publication date

  • November 9, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3207176

Digital Object Identifier (DOI)

  • 10.1016/j.bpj.2011.09.037

PubMed ID

  • 22067146

Additional Document Info

start page

  • 2092

end page

  • 101

volume

  • 101

number

  • 9