Interaction of the maturation protein of the bacteriophage MS2 and the sex pilus of the Escherichia coli F plasmid

Timothy J Spankie,Alexe L Haywood,Tania Dottorini,Paul A Barrow,Jonathan D Hirst

doi:10.1016/j.jmgm.2020.107723

Timothy J Spankie, Alexe L Haywood + Show 3 more

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https://doi.org/10.1016/j.jmgm.2020.107723

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Abstract

One promising strategy to combat antimicrobial resistance is to use bacteriophages that attach to the sex pili produced by transmissible antimicrobial resistance (AMR) plasmids, infect AMR bacteria and select for loss of the AMR plasmids, prolonging the life of existing antimicrobials. The maturation protein of the bacteriophage MS2 attaches to the pili produced by Incompatibility group F plasmid-containing bacteria. This interaction initiates delivery of the viral genetic material into the bacteria. Using protein-protein docking we constructed a model of the F pilus comprising a trimer of subunits binding to the maturation protein. Interactions between the maturation protein and the F pilus were investigated using molecular dynamics simulations. In silico alanine scanning and in silico single-point mutations were explored, with the longer term aim of increasing the affinity of the maturation protein to other Incompatibility group pili, without reducing the strength of binding to F pilin. We report our computational findings on which residues are required for the maturation protein and F pilin to interact, those which had no effect on the interaction and the mutations which led to a stronger interaction.

Highlights

Despite the morphological simplicity of bacteria, the cell structure is well developed, having unique biological structures and widely known pathogenicity.[6]
In our study the interaction between the F-specific bacteriophage MS2 maturation protein and the sex pilus produced by the F plasmid E. coli is examined
We have developed a model of the maturation protein - F pilin protein-protein complex using three subunits of the F pilus

Summary

Introduction

Despite the morphological simplicity of bacteria, the cell structure is well developed, having unique biological structures and widely known pathogenicity.[6]. In our study the interaction between the F-specific bacteriophage MS2 maturation protein and the sex pilus produced by the F plasmid E. coli is examined The bacteriophage consists of 89 coat protein dimers arranged in a T = 3 icosahedral lattice.[24] Three conformations are adopted, denoted A, B and C which form a symmetric CC dimer and an asymmetric AB dimer In these coat proteins there is a crucial ’FG’ loop region (residues His[55] to Ser78) which plays a key role in the self-assembly of the caspid.[25,26,27] Embedded into the caspid wall is a single copy of the maturation protein which binds to the pilus and protects the ssRNA genome inside. A 50 ns molecular dynamics (MD) simulation found that pores in the caspid wall allow transport of ions and water in both directions.[26] a b

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