mosorio91.bsky.social

mosorio91.bsky.social

@mosorio91.bsky.social

64 followers133 following10 posts

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Tung Le
@tunglejic.bsky.social

@biorxiv-microbiol.bsky.social Who knew ParB-CTPase fold can kill!!! A protein fold best known for segregating chromosomes…can be transformed into a potent antibacterial toxin in some plant and animal pathogens. www.biorxiv.org/content/10.6...

biorxiv.orgRepurposing a chromosome segregation ParB-CTPase fold into an ATPase toxin for contact-dependent growth inhibition in plant and animal pathogensBacterial competition drives the evolution of antibacterial mechanisms, yet how new activities arise remains poorly understood. A major route to innovation is the reuse of pre-existing genetic systems, whereby conserved protein modules are repurposed in new biological contexts to generate new capabilities. Here, we show that the ParB-CTPase fold, a conserved nucleotide-binding module best known for its role in chromosome segregation, can be functionally repurposed as an antibacterial toxin. We identify ToxB, a ParB-like domain embedded within the polymorphic toxin region of contact-dependent inhibition systems and show that it functions as a potent antibacterial effector. Structural and biochemical analyses reveal that ToxB retains the core architecture of the ParB-CTPase fold but lacks DNA-binding capability and preferentially binds ATP. This shift in nucleotide specificity underpins a distinct mode of action, in which ATP binding and hydrolysis trigger rapid nucleoid compaction, chromosome segregation defects, oxidative stress, cell chaining, and ultimately cell lysis. ToxB also exhibits toxic activity in plant cells, suggesting that it targets conserved cellular processes. Together, these findings provide direct experimental evidence that the ParB-NTPase fold is biologically versatile and can be repurposed for biological roles fundamentally distinct from its ancestral function in DNA segregation. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, https://ror.org/029chgv08, 221776/Z/2/Z, 227755/Z/23/Z Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X01097X/1 Diamond Light Source, MX32728
mosorio91.bsky.social
@mosorio91.bsky.social

It was an honor to participate in this event. I had the opportunity to present my postdoctoral work and interact with the exceptional scientific community at the Helmholtz Munich.

Helmholtz Munich@helmholtzmunich.bsky.social

🌍 The #HelmholtzMunich Talent Forum 2025 brought together exceptional early-career scientists in #epigenetics & nucleic acids research to foster exchange, collaboration & research excellence. 👩‍🔬👨‍🔬 👉 t1p.de/3dsix @boyanbonev.bsky.social @epihmgu.bsky.social #TalentForum

mosorio91.bsky.social
@mosorio91.bsky.social

The final version of our ParA-ParB paper is online. Thanks to the reviewers for their input and to all the authors for their hard work. www.nature.com/articles/s41...

nature.comMolecular basis of ParA ATPase activation by the CTPase ParB during bacterial chromosome segregation - Nature CommunicationsParABS systems partition chromosomal DNA and low-copy plasmids in bacteria. Here, the authors elucidate the mode of interaction between ParA and ParB and clarify how ParB stimulates the ATPase activity of ParA to drive the segregation process.
mosorio91.bsky.social
@mosorio91.bsky.social

I can only recommend @thanbichlerlab.bsky.social as a mentor. You’ll do great science in a friendly environment with great colleagues and live in beautiful Marburg. Apply now!

Martin Thanbichler@thanbichlerlab.bsky.social

#Postdoc position - at the University of Marburg (Germany), funded within our ERC Advanced Grant "C-SWITCH" Focus: CTP-dependent molecular switches as a new principle of cellular regulation in bacteria (including bacteriophages) Apply by 04 May: stellenangebote.uni-marburg.de/jobposting/2...

mosorio91.bsky.social reposted

Martin Thanbichler
@thanbichlerlab.bsky.social

Interested in the bacterial ParABS DNA segregation system? Then have a look at our latest preprint... 🧬 Thanks to the Hennig and Bange groups for the great collaboration! doi.org/10.1101/2025...

doi.orgMolecular basis of ParA ATPase activation by the CTPase ParB during bacterial chromosome segregationDNA segregation by bacterial ParABS systems is mediated by transient tethering interactions between nucleoid-bound dimers of the ATPase ParA and centromere (parS)-associated complexes of the clamp-for...
mosorio91.bsky.social
@mosorio91.bsky.social

I’m very happy to share our latest work on the ParABS system. We investigated the dynamic interaction between the ATPase ParA and the CTPase ParB mediating chromosome segregation in Myxococcus xanthus. I would like to thank all the people involved.

bioRxiv Microbiology@biorxiv-microbiol.bsky.social

Molecular basis of ParA ATPase activation by the CTPase ParB during bacterial chromosome segregation https://www.biorxiv.org/content/10.1101/2025.03.14.642875v1

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mosorio91.bsky.social
@mosorio91.bsky.social

We used Hydrogen/deuterium exchange mass spectrometry to show that ParB and nsDNA bind cooperatively to ParA and act synergistically to induce conformational changes in the catalytic site of ParA that correlate with the activation of its ATPase activity.

mosorio91.bsky.social
@mosorio91.bsky.social

We explored the role of the conserved arginine residue in the ParA-interacting motif of ParB and propose that rather than acting as an arginine finger, it interacts with negatively changed residues on ParA, likely promoting structural changes at its catalytic center required for ATP hydrolysis

mosorio91.bsky.social
@mosorio91.bsky.social

I’m very happy to share our latest work on the ParABS system. We investigated the dynamic interaction between the ATPase ParA and the CTPase ParB mediating chromosome segregation in Myxococcus xanthus. I would like to thank all the people involved.

bioRxiv Microbiology@biorxiv-microbiol.bsky.social

Molecular basis of ParA ATPase activation by the CTPase ParB during bacterial chromosome segregation https://www.biorxiv.org/content/10.1101/2025.03.14.642875v1

mosorio91.bsky.social
@mosorio91.bsky.social

We used an integrative structural approach combining AF modeling, X-ray crystallography, and NMR spectroscopy to map the interaction interfaces on both proteins. We found that the N-terminal ParA-binding motif of ParB binds at the ParA dimer interface, near its catalytic center.

mosorio91.bsky.social
@mosorio91.bsky.social

Moreover, we show that ParB clamps preferentially interact with ParA in their closed CTP-bound conformation ensuring that only partition complex-associated ParB molecules can effectively interact with nucleoid-bound ParA dimers.

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