Prokaryotic Cytoskeletons and other Molecular Machines

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

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SMC DNA loading complex resolved

A new structure reveals that likely all SMC complexes entrap DNA topologically and that during DNA loop extrusion DNA is topologically entrapped.

Ring-like structural maintenance of chromosomes (SMC) complexes are crucial for genome organisation and operate through mechanisms of DNA entrapment and loop extrusion. We explored the DNA loading process of the bacterial SMC complex MukBEF.

Using electron cryomicroscopy (cryo-EM), we demonstrated that ATP binding opens one of MukBEF's three potential DNA entry gates, exposing a DNA capture site that positions DNA at the open neck gate. We discovered that the gp5.9 protein of bacteriophage T7 blocks this capture site by DNA mimicry, thereby preventing DNA loading and inactivating MukBEF.

We propose a comprehensive and unidirectional loading mechanism in which DNA is first captured at the complex's periphery and then ingested through the DNA entry gate, powered by a single cycle
of ATP hydrolysis.

These findings illuminate a fundamental aspect of how ubiquitous DNA organisers are primed for genome maintenance and demonstrate how this process can be disrupted by viruses.

Bürmann F., Clifton B., Koekemoer S., Wilkinson O.J., Kimanius D., Dillingham M.S., Löwe J., "Mechanism of DNA entrapment by the MukBEF SMC complex and its inhibition by a viral DNA mimic", Cell 188, 2465-2479 (2025), Supplement, Movie

Welcome! We aim to discover the molecular mechanisms that underpin important cell biological functions .

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. They share their three-dimensional structures of the subunits, similar protofilaments and polymerisation linked to nucleotide hydrolysis. These discoveries started the field of prokaryotic cytoskeletons.

In fact, the nucleotide-driven dynamics of these polymers make them immensely useful since they are used by cells to generate movement. They can be regarded as one-dimensional motors, hence we termed them cytomotive (Wagstaff et al., 2023).

As a continuation of our work on cytomotive filaments, we now concentrate on bacterial cell division, the process that makes two cells out of one. In many bacteria the process is organised by tubulin-like FtsZ. We use cryo-EM on reconstituted division complexes, electron cryotomography (cryo-ET) of cells and in vitro reconstitution experiments with which we aim to recreate cell division in liposomes.

Another focus of the group are Structural Maintenance of Chromosomes (SMC) proteins and we are deciphering the mechanisms of eukaryotic cohesin and condensin in sister chromatid cohesion and loop extrusion.

We very much enjoy working at the MRC Laboratory of Molecular Biology (LMB), it is an amazing place for discovering how life works!

Do 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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