The Bacterial Cytoskeleton and other Molecular Machines

Jan Löwe's group at the MRC Laboratory of Molecular Biology

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Divisome core complex resolved

Finally, after many years, we have solved the structure of the divisome core complex by cryo-EM.

Cell division in the vast majority of bacteria depends on the synthesis of new cell wall peptidoglycan and is catalysed by the divisome. The divisome is organised on the inside of the cell by the tubulin-like protein FtsZ that polymerises and forms the main component of the Z-ring.

Central to the divisome is the peptidoglycan-synthesising protein complex FtsWI, which is regulated by the heterotrimer FtsQBL. We have now resolved the cryo-EM structure of the activated divisome catalytic core complex FtsWIQBL from Pseudomonas aeruginosa at 3.7 Å resolution.

We are able to provide molecular mechanisms of a multitude of cell division phenotypes of known mutations and reveal a large conformational switch between presumably inactive and active states of the FtsWI core enzymes.

This is the beginning of a longer journey into the molecular mechanism of FtsZ-based bacterial cell division, which we will now be able to uncover with ever more complete divisome complexes and also by imaging these machines directly in cells, using electron tomography.

divisome small

Käshammer L., van den Ent F., Jeffery M., Jean N.L., Hale V.L., Löwe J., "Cryo-EM structure of the bacterial divisome core complex and antibiotic target FtsWIQBL", Nature Microbiology 8, 1149-1159 (2023)

Welcome to the group "The Bacterial Cytoskeleton and other Molecular Machines" at the Laboratory of Molecular Biology of the Medical Research Council, UK. We investigate the structure and function of filamentous proteins in bacteria that participate in phenomena such as cell division, chromosome segregation, cell wall synthesis and intracellular motility. We also decipher the mechanisms of other molecular machines, including but not restricted to SMC complexes such as cohesin and condensin.

Until the mid 1990s it was thought that bacteria lack a cytoskeleton

It was thought that homologues of actin and tubulin (forming F-actin and microtubules in eukaryotes, respectively) are missing from all bacteria and archaea.

In the past, we could show that FtsZ and MreB, present in a large number of bacteria, are clear homologues of eukaryotic tubulin and actin, respectively. This is supported by a similar three-dimensional structure of the monomer subunits, similar protofilaments and similar properties that link (de-) polymerisation to nucleotide hydrolysis.

In fact, the nucleotide-driven dynamics of these polymers make them immensely useful for the majority of living organisms since polymer growth and disassembly may be used by cells to generate force. Indeed, they can often be regarded as one-dimensional motors, hence we termed them cytomotive. For further reading we suggest our review in Nat Rev Microbiology (2017).

For our investigations into the bacterial cytoskeleton we employ a multi scale approach that involves X-ray crystallography for the visualisation of atoms in molecules, electron microscopy for imaging molecules in filaments and whole, frozen cells (electron cryotomography) and light microscopy for visualising the dynamics of cytomotive filaments and cells.

In addition to our work on cytomotive filaments, we are deciphering the mechanisms of eukaryotic cohesin in a collaboration with Kim Nasmyth in Oxford. We have also worked on bacterial dynamin, Lon protease, and a large variety of cytoskeleton-related proteins. One of the most active areas at the moment are the ParMRC and TubZRC systems for bacterial plasmid segregation that have proved invaluable in deciphering some of the basic principles of cytomotive filaments because of their relative simplicity.

We very much enjoy working at the MRC Laboratory of Molecular Biology and we would like to encourage you to read about this amazing place on our institute's websites.

Feel free to get in touch if you are interested in work opportunities here, we regularly have summer students stay for 3-6 months and PhD application deadlines are usually in December. Postdoc applications are welcome at any time.

Jan Löwe

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