Journal Article

Native-like membrane models of E. coli polar lipid extract shed light on the importance of lipid composition complexity

Horner, Andreas, Pluhackova, Kristyna

2021

Overview

Background Lipid-protein interactions stabilize protein oligomers, shape their structure, and modulate their function. Whereas in vitro experiments already account for the functional importance of lipids by using natural lipid extracts, in silico methods lack behind by embedding proteins in single component lipid bilayers. However, to accurately complement in vitro experiments with molecular details at very high spatio-temporal resolution, molecular dynamics simulations have to be performed in natural(-like) lipid environments. Results To enable more accurate MD simulations, we have prepared four membrane models of E. coli polar lipid extract, a typical model organism, each at all-atom (CHARMM36) and coarse-grained (Martini3) representations. These models contain all main lipid headgroup types of the E. coli inner membrane, i.e., phosphatidylethanolamines, phosphatidylglycerols, and cardiolipins, symmetrically distributed between the membrane leaflets. The lipid tail (un)saturation and propanylation stereochemistry represent the bacterial lipid tail composition of E. coli grown at 37 ∘ C until 3/4 of the log growth phase. The comparison of the Simple three lipid component models to the complex 14-lipid component model Avanti over a broad range of physiologically relevant temperatures revealed that the balance of lipid tail unsaturation and propanylation in different positions and inclusion of lipid tails of various length maintain realistic values for lipid mobility, membrane area compressibility, lipid ordering, lipid volume and area, and the bilayer thickness. The only Simple model that was able to satisfactory reproduce most of the structural properties of the complex Avanti model showed worse agreement of the activation energy of basal water permeation with the here performed measurements. The Martini3 models reflect extremely well both experimental and atomistic behavior of the E. coli polar lipid extract membranes. Aquaporin-1 embedded in our native(-like) membranes causes partial lipid ordering and membrane thinning in its vicinity. Moreover, aquaporin-1 attracts and temporarily binds negatively charged lipids, mainly cardiolipins, with a distinct cardiolipin binding site in the crevice at the contact site between two monomers, most probably stabilizing the tetrameric protein assembly. Conclusions The here prepared and validated membrane models of E. coli polar lipids extract revealed that lipid tail complexity, in terms of double bond and cyclopropane location and varying lipid tail length, is key to stabilize membrane properties over a broad temperature range. In addition, they build a solid basis for manifold future simulation studies on more realistic lipid membranes bridging the gap between simulations and experiments.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adaptation / Antibiotics / Aquaporins / Bacteria / Binding sites / Biomedical and Life Sciences / Cardiolipin / Cardiolipins - chemistry / Cell division / Cell Membrane - chemistry / CHARMM36 / Complexity / Composition / Compressibility / Cyclopropane / E coli / E. coli polar lipid extract / Embedding / Escherichia coli / Escherichia coli - chemistry / Experiments / Fatty acids / Life Sciences / Lipid bilayers / Lipid Bilayers - chemistry / Lipid composition / Lipid membranes / Lipid-protein interactions / Lipids / Martini / Membrane fluidity / Membrane lipids / Membranes / Molecular dynamics / Molecular Dynamics Simulation / Molecular dynamics simulations / Monomers / Oligomers / Permeability / Phosphatidylethanolamines - chemistry / Phosphatidylglycerol / Phosphatidylglycerols - chemistry / Physiological aspects / Protein composition / Protein interaction / Protein research / Protein structure / Protein-protein interactions / Proteins / Research Article / Simulation / Stereochemistry / Structure / Tails / Temporal resolution / Water permeability