Diorge Souza

A conserved archaeal ribosome-associated factor linking bacterial hibernation and eukaryotic energy sensing pubmed.ncbi.nlm.nih.gov/41757010/ #cryoEM

Another paper on a topic we never worked on before: a new ribosomal hibernation!

Under the leadership of the super-postdoc Diorge, Davis Lab (ribo-cryoEM master), and @vikramalva.bsky.social (protein-evo whisperer), we identified AHA (not the song, but archaeal hibernation AMPKγ factor).

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A fantastic position! The dream place to do science! 🤩

Thank you, Ricardo! 😃

Thank you, Javi!!!

Very cool work led by @diorgeps.bsky.social from the labs of @archaeon-alex.bsky.social & Joey Davis (MIT)!

They solved the Haloferax volcanii ribosome and characterize AHA, a conserved archaeal hibernation factor.

With several recent related preprints, it’s an exciting moment for the field!

And Hib (same domain composition of AHA):
www.biorxiv.org/content/10.1...

ARC-A/ARC-P: www.biorxiv.org/content/10.6...

SriA-D: www.biorxiv.org/content/10.6...

Structure of an archaeal ribosome reveals a divergent active site and hibernation factor - Nature Microbiology Sequence and structural analyses reveal a divergent peptidyl transferase centre and a hibernation factor in archaea.

And here are links to the other recent manuscripts describing related archaeal hibernation factors. Thrilled to be part of this wave of discoveries!
Dri: www.nature.com/articles/s41...

Huge shout out to the amazing co-authors
Mira May
@jacksoncarrion.bsky.social
@vikramalva.bsky.social

You are all superstars ⭐

In other words: ancient ribosome hibernation machinery and the eukaryotic AMPK energy-sensing pathway may share common evolutionary roots. Energy-responsive translational shutdown might be a deeply ancestral strategy.

This suggests something remarkable: archaeal ribosome hibernation factors may directly link translational silencing to cellular energy sensing. Our phylogenetic analyses indicate that AMPKγ evolved from the archaeal CBS-tetrad lineage that includes AHA.

The N-terminal 4×CBS domain binds two AMP molecules. Structurally and evolutionarily, it is related to AMPKγ, the main energy sensor in eukaryotes.

The C-t domain is homologous to HPF, previously described as a highly conserved bacterial hibernation factor.
HPF-like domains are widespread in both bacteria and archaea + phylogeny → likely present in the Last Universal Common Ancestor.

This may be the first universal ribosome hibernation module.

AHA is built from two evolutionarily distinct modules: A C-terminal HPF-like domain that binds the small subunit and an N-terminal 4×CBS domain that inserts into the large subunit’s peptidyl transferase center.

Functionally, deleting AHA is costly. ΔAHA cells:
• show reduced viability in stationary phase
• lose ribosomal proteins
• struggle to regrow after starvation
• are outcompeted by wild type

All consistent with a bona fide hibernation factor

Using cryoEM directly on cell lysates, we found AHA bound at the functional core of the ribosome, blocking the A- and P-tRNA sites and the mRNA channel (fully incompatible with translation)

And then… an avalanche. Over the past few months, several preprints have described new archaeal ribosome hibernation factors. It’s an exciting moment for the field! I’ll link all of them at the end of this thread.

Ribosome hibernation helps cells survive stress by reversibly silencing translation and protecting ribosomes from degradation.

It’s well studied in bacteria and eukaryotes; but until very recently, archaeal hibernation remained largely mysterious.

A new preprint from the @archaeon-alex.bsky.social and Joey Davis (MIT) labs! We solved the structure of the ribosome from the archaeon Haloferax volcanii and discovered a new highly conserved ribosome hibernation factor that we named AHA (AMPKγ–HPF from Archaea) 🧵⬇️ www.biorxiv.org/content/10.6...

So happy to see this come together! Huge congratulations to my friend @javierespadas.bsky.social and everyone involved. Amazing job!

Javier has done beautiful work (following on from the study he did with Diorge Souza), showing how Asgard Escrt-III likely cut membranes. The answer: with Hofund.

Fantastic work from Javier @javierespadas.bsky.social in collaboration with @buzzbaum.bsky.social and @kaksonen.bsky.social labs, thank you Chris Toret, thank you Diorge @diorgeps.bsky.social!

Molecular basis for cellular compartmentalization by an ancient membrane fission mechanism The emergence of cell compartmentalization depends on membrane fission to create the endomembrane compartments. In eukaryotes, membrane fission is commonly executed by ESCRT-III, a protein complex con...

New preprint from the lab!!🎉
We show that Asgard archaea ESCRT-III proteins can trigger membrane fission and reveal its molecular mechanism, offering clues to how these cells may have built internal compartments. But do these organisms even have these compartments?
www.biorxiv.org/content/10.1...

Extremely happy to see our work finally out!🎉 Great collaboration between @rouxlab.bsky.social @buzzbaum.bsky.social labs and a real pleasure to work and share co-first authorship with incredible scientists and friends @diorgeps.bsky.social @sami-c.bsky.social. Big thanks to the rest of the authors!

Evolution, structure and membrane remodelling function of the ESCRT-III superfamily in eukaryotes and their closest relatives Asgard archaea. The two subfamilies, B-type and A-type, have distinct structural properties to perform sequential steps of the membrane remodelling pathway.

New research on ancient Asgard archaeal ESCRT-III proteins reveals evolutionary secrets of membrane remodelling.
Diorge Souza, Javier Espadas and Sami Chaaban, investigated the ESCRT-III proteins with Buzz Baum and Aurelien Roux.
Read more: www2.mrc-lmb.cam.ac.uk/asgard-archa...
#LMBResearch (1/2)

ESCRT-III is an ancient complex, present in Archaea, with only two proteins and all membrane remodelling functions. Great work by @javierespadas.bsky.social, @diorgeps.bsky.social, @sami-c.bsky.social, thanks to the @buzzbaum.bsky.social lab! Drawing by Julie Polge.
www.science.org/doi/10.1126/...

Thanks Harry!

Great Oriol! Congrats!