Abstract
The outer membrane of Gram-negative bacteria has a highly complex asymmetrical architecture, containing a mixture of phospholipids in the inner leaflet and almost exclusively lipopolysaccharide (LPS) molecules in the outer leaflet. In E. coli, the outer membrane contains a wide range of proteins with a β barrel architecture, that vary in size from the smallest having eight strands to larger barrels composed of 22 strands. Here we report coarse-grained molecular dynamics simulations of six proteins from the E. coli outer membrane OmpA, OmpX, BtuB, FhuA, OmpF, and EstA in a range of membrane environments, which are representative of the in vivo conditions for different strains of E. coli. We show that each protein has a unique pattern of interaction with the surrounding membrane, which is influenced by the composition of the protein, the level of LPS in the outer leaflet, and the differing mobilities of the lipids in the two leaflets of the membrane. Overall we present analyses from over 200 μs of simulation for each protein.
Highlights
The outer membrane proteins (Omps) of Gram-negative bacteria perform a wide range of functions including signaling, host cell adhesion, catalysis of crucial reactions, and transport of solutes/nutrients into and out of the cell
We have shown that the six outer membrane proteins we have studied here, OmpA, OmpX, FhuA, BtuB, OmpF, and EstA, have unique patterns of interaction with the outer membrane
In the inner leaflet we find that cardiolipin is depleted within the vicinity of all six Omps, in contrast to findings by ourselves and others that cardiolipin is enriched near some bacterial inner membrane proteins
Summary
The outer membrane proteins (Omps) of Gram-negative bacteria perform a wide range of functions including signaling, host cell adhesion, catalysis of crucial reactions, and transport (active and passive) of solutes/nutrients into and out of the cell. We and others have previously shown that inclusion of this biochemical heterogeneity is important for understanding the conformational dynamics of Omps.[4] a thorough study of the interplay between these proteins and their local membrane environment and how this may differ in a protein-dependent manner, such as the study by Tieleman and co-workers in which the “fingerprint” of each protein is identified, has so far not been reported for Omps in Received: October 19, 2018 Published: March 8, 2019 Article their natural lipid environment.[5] One particular technical issue that arises when simulating LPS-containing membranes is that of conversion, given the slowly diffusing nature of the lipids. To identify whether the patterns of Omp orientations and their interactions with the local membrane environment are uniform or dependent upon the protein and/or membrane type, we have performed coarse-grained simulations of six Omps of varying sizes, namely OmpX, OmpA (N-terminal domain), BtuB, FhuA, OmpF, and EstA in outer membrane models that vary in the level of LPS in the outer leaflet. In undertaking this study we have been able to determine the time scales that are required for convergence of various properties of LPScontaining systems; these are significantly longer than those needed for simpler phospholipid membranes
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