@katrinrittinger.bsky.social @thurstonlab.bsky.social

It was a team effort! I’m lucky to have worked with and learnt from knowledgeable, experienced and inspiring supervisors & co-authors, and many more in the Crick and Imperial infection communities. I look forward to the discussions and further study that come from this work 🦠

For this and much much more read the full paper, now available on biorxiv biorxiv.org/content/10.1... 9/11

In infection, SteC without its C-tail was translocated into the host cell just like wild-type, but failed to localise to the tip of the Salmonella and was unable to polymerise actin. This suggests the C-tail localises SteC for efficient kinase activity in the host cell. 8/11

Meanwhile the C-tail of SteC, which is predicted to be poorly structured, is dispensable for SteC activity in vitro and is not required for actin polymerisation in transfected human cells. So what is the role of the C-tail? 7/11

Furthermore, Salmonella infected into human cells requires phosphorylation of SteC at S379 for its functions to be seen. 6/11

To our surprise, we found that SteC is activated through phosphorylation by a host kinase at serine 379. Without this, SteC is less able to phosphorylate its known substrates in vitro, and is unable to polymerise actin in human cells transfected with the steC gene. 5/11

AlphaFold2 predicts the structure of SteC to contain a minimal kinase domain, lacking key expected features compared to known kinases, and containing a poorly structured C-tail. Despite this, SteC still functions as a kinase. How? 4/11

So what better enzyme to study than SteC, a kinase found in pathogenic strains of Salmonella? Once Salmonella enters the host cell, it translocates SteC into the host cytoplasm via its type 3 secretion system, where it phosphorylates host proteins leading to actin polymerisation. 3/11

Kinases, arguably the best studied enzyme class, add phosphate onto target proteins, usually at serine, threonine or tyrosine residues. This process is called phosphorylation. 2/11