Panos Spatharas

Panos Spatharas

@pspatharas.bsky.social

PhD student in structural biology at EMBL

42 followers50 following19 posts

Panos Spatharas
@pspatharas.bsky.social

10/11 Together, our findings explain how retrons respond to single-site DNA modifications and showcase how the same bacterial defence effector can diversify its toxicity during evolution.

Panos Spatharas
@pspatharas.bsky.social

8/11 This led us to a broader question. Why are some RcaT homologues toxic for the host, while others defend against phages without being toxic on their own? Does their capacity to assemble beyond a dimer explain this difference?

Panos Spatharas
@pspatharas.bsky.social

9/11 Across the homologues we examined, RcaTs that form tetramers or larger assemblies are toxic and occupy distinct phylogenetic clades from non-toxic, dimeric RcaTs. This links differences in toxicity to an intrinsic protein property: the capacity to oligomerise.

Panos Spatharas
@pspatharas.bsky.social

6/11 All these assemblies form through the same dimer–dimer interface (a), which was occluded in the intact retron complex. Mutations that disrupt this interface abolish RcaT toxicity (b), showing that assembly beyond a dimer is essential for its activity.

Panos Spatharas
@pspatharas.bsky.social

7/11 Together, our findings support a model in which methylation promotes msDNA disengagement, exposing the previously occluded dimer–dimer interface. This allows RcaT tetramerisation and activation, coupled to retron complex disassembly.

Panos Spatharas
@pspatharas.bsky.social

2/11 Retrons produce multicopy single-stranded DNA (msDNA) to monitor DNA-targeting phage proteins during infection. While activation by msDNA degradation is easier to envision, how subtle chemical modifications such as methylation activate retrons has remained enigmatic.

Panos Spatharas reposted

Typas Lab
@typaslab.bsky.social

How does a single methyl group activate bacterial defence? Our new preprint, led by @pspatharas.bsky.social in collaboration with the group of @matthiaswilmanns.bsky.social, explains how a single DNA methylation event activates large retron assemblies. www.biorxiv.org/content/10.6...

biorxiv.orgSingle-site DNA methylation activates retron defence by enabling effector tetramerisationRetrons are unique among bacterial defence systems in using DNA to sense phage infection. They achieve this by producing multicopy single-stranded DNA (msDNA) that monitors the activity of DNA-targeti...

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