Self-association of MreC as a regulatory signal in bacterial cell wall elongation

Alexandre Martins,Andréa Dessen,Daniel Maragno Trindade,Guy Schoehn,Viviana Job,Lionel Imbert,Ina Attrée,Mayara M Miyachiro,Fernanda Rodrigues-Costa,Caíque C Malospirito,Manon Janet-Maitre,Leandro F Estrozi,Carlos Contreras-Martel

doi:10.1038/s41467-021-22957-9

Abstract

The elongasome, or Rod system, is a protein complex that controls cell wall formation in rod-shaped bacteria. MreC is a membrane-associated elongasome component that co-localizes with the cytoskeletal element MreB and regulates the activity of cell wall biosynthesis enzymes, in a process that may be dependent on MreC self-association. Here, we use electron cryo-microscopy and X-ray crystallography to determine the structure of a self-associated form of MreC from Pseudomonas aeruginosa in atomic detail. MreC monomers interact in head-to-tail fashion. Longitudinal and lateral interfaces are essential for oligomerization in vitro, and a phylogenetic analysis of proteobacterial MreC sequences indicates the prevalence of the identified interfaces. Our results are consistent with a model where MreC’s ability to alternate between self-association and interaction with the cell wall biosynthesis machinery plays a key role in the regulation of elongasome activity.

Highlights

The elongasome, or Rod system, is a protein complex that controls cell wall formation in rodshaped bacteria
Proteins that are involved in PG biosynthesis associate in dynamic multi-membered complexes that regulate cell division and cell wall elongation, and their inhibition or deregulation can lead to defects in cell shape, impaired growth, and often cell wall lysis and death[1,2]
In order to modulate lateral peptidoglycan biosynthesis, the elongasome must have a mechanism to sense whether all protein partners are correctly positioned

Summary

Introduction

The elongasome, or Rod system, is a protein complex that controls cell wall formation in rodshaped bacteria. MreC is a membrane-associated elongasome component that co-localizes with the cytoskeletal element MreB and regulates the activity of cell wall biosynthesis enzymes, in a process that may be dependent on MreC self-association. Our results are consistent with a model where MreC’s ability to alternate between self-association and interaction with the cell wall biosynthesis machinery plays a key role in the regulation of elongasome activity. MreC has been linked to regulation of elongasome activity through the activation of PBP2 and RodA22 and interaction with MreD23, in a process that could be dependent on MreC’s ability to self-associate in an organized fashion in the cell. We show that these interaction regions play a role in MreC’s stability in vivo, further illustrating MreC’s modularity and self-associating capacity that could serve as a regulatory signal in the bacterial cell wall elongation process

Methods

Results

Conclusion