1/11 - With Karin Mitosch and Clément Potel + colleagues in Savitski lab and @typaslab.bsky.social @embl.org, I’m very happy to share our discovery of a hyper-promiscuous phage protein kinase (T7K) which broadly deactivates bacterial defenses! 🦠 www.biorxiv.org/content/10.1... - ThreadSky

tarabartolec.bsky.social • 66 days ago

1/11 - With Karin Mitosch and Clément Potel + colleagues in Savitski lab and @typaslab.bsky.social @embl.org, I’m very happy to share our discovery of a hyper-promiscuous phage protein kinase (T7K) which broadly deactivates bacterial defenses! 🦠
https://www.biorxiv.org/content/10.1101/2024.12.20.629319v1

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tarabartolec.bsky.social•66 days ago

2/11 - T7K has been studied since the 70s w/ a handful of (v. abundant) substrates identified using traditional biochem (SDS-PAGE, radio-labelling, WBs). We studied T7 w/ modern bacterial phosphoproteomics (better sensitivity + specificity) and found a COMPLETELY different story…

tarabartolec.bsky.social•66 days ago

3/11 - T7 infection induced a massive wave of phosphorylation - dependent on T7K! We found that T7K is incredibly promiscuous, exceeding the combined activity of 500+ human kinases in just 5 min! Promiscuity is likely through dual-specificity (S/T & Y) + no sequence motif.

tarabartolec.bsky.social•66 days ago

4/11 - But how do you interpret a kinase’s role if it phosphorylates EVERYTHING? We tried estimating phosphorylation stoichiometry and found that there was some order to the madness - nucleic-acid binding proteins were much more heavily modified than the rest of the proteome.

tarabartolec.bsky.social•66 days ago

5/11 - This is achieved through the protein’s C-terminal domain - a long, highly charged and extended alpha-helical region which resembles a histone tail and binds DNA, which colocalises + focuses the loose-canon kinase’s activity towards nucleic acid-binding proteins.

tarabartolec.bsky.social•66 days ago

6/11 - But the T7K gene was reported to be largely dispensable when T7 infected lab strain K-12. Why keep a hyper-promiscuous kinase around if its function is simply to optimise host takeover (translation, transcription)? Doesn’t this activity also hinder T7’s infection cycle?

tarabartolec.bsky.social•66 days ago

7/11 - The stoichiometry results gave us a major clue as to what was really going on - bacterial anti-phage defense systems often work by sensing and/or targeting the phage’s nucleic acids. Perhaps the kinase can brute-force deactivate bacterial defenses?

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