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How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins

Matthieu Chavent, Anna L. Duncan, Patrice Rassam, Oliver Birkholz, Jean Hélie, Tyler Reddy, Dmitry Beliaev, Ben Hambly, Jacob Piehler, Colin Kleanthous () and Mark S. P. Sansom ()
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Matthieu Chavent: University of Oxford
Anna L. Duncan: University of Oxford
Patrice Rassam: University of Oxford
Oliver Birkholz: University of Osnabrück
Jean Hélie: University of Oxford
Tyler Reddy: University of Oxford
Dmitry Beliaev: University of Oxford
Ben Hambly: University of Oxford
Jacob Piehler: University of Osnabrück
Colin Kleanthous: University of Oxford
Mark S. P. Sansom: University of Oxford

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract The spatiotemporal organisation of membranes is often characterised by the formation of large protein clusters. In Escherichia coli, outer membrane protein (OMP) clustering leads to OMP islands, the formation of which underpins OMP turnover and drives organisation across the cell envelope. Modelling how OMP islands form in order to understand their origin and outer membrane behaviour has been confounded by the inherent difficulties of simulating large numbers of OMPs over meaningful timescales. Here, we overcome these problems by training a mesoscale model incorporating thousands of OMPs on coarse-grained molecular dynamics simulations. We achieve simulations over timescales that allow direct comparison to experimental data of OMP behaviour. We show that specific interaction surfaces between OMPs are key to the formation of OMP clusters, that OMP clusters present a mesh of moving barriers that confine newly inserted proteins within islands, and that mesoscale simulations recapitulate the restricted diffusion characteristics of OMPs.

Date: 2018
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DOI: 10.1038/s41467-018-05255-9

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