Compare panels a and c in figure above.

Thank you! Yes, we had 2 types of samples, fl & slightly truncated, and we personally mostly worked with the latter, which gave a bit lower quality dataset. Also, helical reconstr. didn't work well, so we did 'single partcl' reconstr. of a filament fragment and then foc. ref. of a minimal element.

That's very generous of you. Thanks so much @audeber.bsky.social

I thank also our great labs @cbm-upr4301.bsky.social,
@dunnschool.bsky.social, @igdrennes.bsky.social, @pasteur.fr, & funding sources including @agencerecherche.bsky.social, @erc.europa.eu, @wellcometrust.bsky.social, and @natsmb.nature.com for very constructive revision. I'm sorry if forgetting sb.

A different link to our article if the one in the 1st slide doesn't work: www.nature.com/articles/s41...

I'd also like to highlight a recent publication by @audeber.bsky.social, @enzopoirier.bsky.social, and colleagues showing FAM118B, which they term "SIRal", is essential for innate immune response in mammalian cellular models; they also have great phylogenetic analysis and insights into biochemistry.

FAM118s have long interested Ivan (my postdoc PI), who, like in many other cases, had a good intuition about their importance. They have been a difficult biochemical target, though. We brought in the observation that they homooligomerise into filaments, an insight explored collaboratively here.

I also highlight Andreja for her phylogenetic analysis, Karishma for NAD processing assays, and above all Ivan for his intuition, energy, and generosity. But all authors really!

It was a close collab. with @ahellab.bsky.social, @spartelab.bsky.social, and other teams. All authors were important, but I'd like to highlight Domagoj Baretić and Sophia Missoury (with Franck Coste) for their cryoEM & other assays, and Sebastien Huet and his team for their great optical assays.

In brief, we show that human FAM118s are closer to ancestral bacterial sirtuins than to canonical human SIRTs; that they assemble into filaments in vitro and in cells; that they have NAD processing (likely NAD-hydrolysis) activity; and that mixing two paralogues, FAM118B & FAM118A, boosts activity.

The 7 canonical human sirtuins, SIRT1-SIRT7, are well studied enzymes associated with protein deacetylation activity. However, humans have 2 more poorly characterised sirtuin-fold proteins - FAM118B and FAM118A. Here, we study their evolution, structure, and molecular function.