Interactions of lipids and detergents with a viral ion channel protein: molecular dynamics simulation studies.

Sarah L Rouse,Mark S P Sansom

doi:10.1021/jp505127y

Abstract

Structural studies of membrane proteins have highlighted the likely influence of membrane mimetic environments (i.e., lipid bilayers versus detergent micelles) on the conformation and dynamics of small α-helical membrane proteins. We have used molecular dynamics simulations to compare the conformational dynamics of BM2 (a small α-helical protein from the membrane of influenza B) in a model phospholipid bilayer environment with its behavior in protein–detergent complexes with either the zwitterionic detergent dihexanoylphosphatidylcholine (DHPC) or the nonionic detergent dodecylmaltoside (DDM). We find that DDM more closely resembles the lipid bilayer in terms of its interaction with the protein, while the short-tailed DHPC molecule forms “nonphysiological” interactions with the protein termini. We find that the intrinsic micelle properties of each detergent are conserved upon formation of the protein–detergent complex. This implies that simulations of detergent micelles may be used to help select optimal conditions for experimental studies of membrane proteins.

Highlights

Membrane proteins reside in a complex bilayer environment, containing multiple species of lipids
AT resolution simulations of the self-assembly of DHPC micelles at experimentally relevant detergent concentrations were comparable to small-angle X-ray scattering (SAXS) data,24 implying that this approach may be used to study BM2−DHPC complex formation (Supporting Information Figure S1)
The results of this work enable comparisons to be made between three types of environment for a membrane protein: a simple model phospholipid (DPPC) lipid bilayer, small zwitterionic detergent (DHPC) micelles used in solution NMR experiments, and nonionic, larger detergent (DDM) micelles commonly used in protein purification and X-ray crystallography

Summary

Introduction

Membrane proteins reside in a complex bilayer environment, containing multiple species of lipids. By necessity, most structural and biophysical studies require protein reconstitution into either a simple lipid bilayer or a membrane−mimetic detergent environment. We need to improve our understanding of how experimental conditions may influence the properties of a given membrane protein. Recent successes in membrane protein structural biology and biophysics provide a wealth of experimental data to enable us to explore the effect of environment on their structure. A/M2-TM is a small, tetrameric, α-helical membrane protein, the structure of which has been determined by X-ray crystallography, by solution NMR, and by solid-state NMR4 under a range of conditions.. We may expect similar observations to be made for a wider range of membrane proteins as the number of deposited structures continues to expand.

Methods

Results

Conclusion