Lorenz Grundmann

I am incredibly excited to share that I will start my independent lab at the @unidue-zmb.bsky.social at the @unidue.bsky.social as Junior Professor of Cellular Biochemistry. Research in my lab has the goal to decipher the ubiquitin code!
There are multiple open positions!
(1/3)

Long in the making, but happy to present the Chlamydomonas chlororibosome!
Cryo-ET🔬reveals a large new domain on the small subunit, built from multiple extensions in conserved ribosomal proteins.
bioRxiv 📖: shorturl.at/q44tG
This suggests greater chlororibosome diversity than expected!
1/n 🧵

Please share!
My group at @zmbp-tuebingen.bsky.social is offering a post-doctoral position (4 years). We look for a structural biologist with experience in Cryo-EM/Cryo-ET to investigate the mechanisms of host invasion by pathogenic fungi. Deadline February 28th!
uni-tuebingen.de/universitaet...

Formation & function of #MembranelessOrganelles! #CryoET structures of #proteasome storage granules inside cells!
Read our paper @cp-cell.bsky.social!

❕Publication: doi.org/10.1016/j.ce...
❕Press Release: www.biochem.mpg.de/en/pressroom

@uoftmedicine.bsky.social
@erc.europa.eu #UPSmeetMet

Big congratulations and a huge thank you to everyone involved. I am especially greatful for the great collaboration with the shared first author Ying Zhang who was doing the biochemical experiments and handled the yeast.

These findings provide key insight into cotranslational protein folding and proteostasis in eukaryotic cells, resolve the cotranslational cycle of Ssb, and support a unified model integrating prior structural and biochemical data.

Further, we show that initial recruitment of Ssb to the ribosome is independent of direct interaction with RAC but is stabilized by engagement with the NC accompanied by ATP hydrolysis.
This is a criminally short summary of many experiments, please check the paper if you want to know more 😜

Point mutations not only verified our model, but also established this as the interface which is engaged by Ssb in the precatalytic ATP bound state and where Ssb in the ADP state remains bound in the post catalytic ADP state.

We identified Rpl25 as the major interaction site, which was resolved to ~4Å. Being able to assign side chains, we further observed several charged interactions governing this interaction. This was our key finding, which allowed us to decipher the early events of the Ssb cotranslational cycle.

We modeled Met-elongator tRNA base pairing to the final AUG codon and the nascent chain in the exit tunnel. Owing to limited Ssb–SBD-β resolution due to flexibility, the bound NC was only apparent in low-pass filtered maps.

Ending up with just ~14K and ~33K particles we solved the structure of RNC-Ssb in the ADP state in two conformations called S1 and S2. Global resolution was estimated at 2.8Å and 3.0Å for S1 and S2 state respectively. Local resolution of the 80S-Ssb interface, however, was limited to 4-10Å.

Therefore, we started to iteratively classify our particles using increasingly tighter masks. Due to our particle numbers dropping fast, we needed a lot of data. Backfilling our Krios queue, we finally collected >54.000 micrographs.

Focusing on this stalled ribosome population, masked classifications began to converge, and we were able to identify the density as Ssb’s C-terminal substrate binding domain (SBD). With <25 kDa the SBD was too small for local refinements severely limiting the local resolution of the SBD.

The silver bullet was to assess global heterogeneity first. We used cryoDRGN and analyzed the landscape analysis. We found that non-rotated ribosomes with a P-site tRNA and a density corresponding to a trailing ribosome (Figure, Cluster 1), were ever so slightly enriched in Ssb occupancy.

In the initial consensus reconstructions, we noted a small, very weak density close to the exit tunnel in low-pass filtered, weakly thresholded maps. Owing to its low occupancy, masked classification in CS or RELION did not permit further subdivision of the particle stack.
- Figure not published -

We expressed a truncated Flag-Pgk(1-70) mRNA without a stop codon in a yeast in-vitro system with added recombinant Ssb. Thus, we were able to enrich stalled RNC using the nascent chain's (NC) N-terminal Flag tag and prepare cryoEM grids.

To close this knowledge gap, we turned to the yeast Hsp70 Ssb. First, we (@haselbachlab.bsky.social, @impvienna.bsky.social in collaboration with the Rospert group @uni-freiburg.de ) started working on cryoEM structures of ribosome-nascent-chain-complexes (RNC) cotranslational engaged with Ssb.

Coupling ribosomal translation to cotranslational folding is essential for cellular homeostasis. In eukaryotes, this process relies on Hsp70 and its J-domain cochaperone RAC, but how Hsp70 activity is coordinated with translation remains unclear.

Check out our new paper in @natcomms.nature.com .com where we used #cryoEM together with biochemical and mutational analyses investigated the cotranslational protein folding by Ssb in yeast.

Publication: doi.org/10.1038/s41467-025-67685-6

Check below for the cryoEM centric feed. 👇

Have a look at our new structure of co translational folding in yeast. This is collaborative work initialized by the Rospert lab from the @uni-freiburg.de. Structural work has been done by the amazing @lgrundmann.bsky.social Stay tuned for the next ribosome paper from him, following very soon.

A comprehensive view on r-protein binding and rRNA domain structuring during early eukaryotic ribosome formation Abstract. Formation of the eukaryotic ribosomal subunits follows a strict regime to assemble ribosomal proteins (r-protein) with ribosomal RNAs (rRNA) whil

And the 4th paper in this week contribution from our lab tells about ribosome biogenesis in yeast. A follow-up story from our wonderful collaborators in Graz - the Bergler Lab. Structural work was again done by the amazing @lgrundmann.bsky.social: academic.oup.com/nar/article/...

I didn't realize. They nonetheless ended up in my stomach - so tasty :)

One month later and still thinking about the great science and conversations from the 8th Austrian Cryo-EM Symposium 🧊🔬

Huge thanks to all who joined - let’s make next year even bigger!

cryoem-symposium.pages.ist.ac.at/invited-spea...

New paper alert! Scientists in Clemens Plaschka’s lab at the IMP and @juliusbrennecke.bsky.social's lab at
@imbavienna.bsky.social solved a decade-old puzzle, uncovering how the information molecule mRNA travels from the cell’s nucleus to its periphery. More: bit.ly/4nHcvys

just in time for the opening of the @hohmannulrich.bsky.social group at @imbmainz.bsky.social
what started as a project on how cells export piRNA precursors, ended up as a tour de force in mRNA export. truly wonderful collaboration with @plaschkalab.bsky.social at the @viennabiocenter.bsky.social

Electrostatic changes enabled the diversification of an exocyst subunit via protein complex escape - Nature Plants The evolutionary diversification of an exocyst subunit was enabled by electrostatic shifts leading to its dissociation from the ancestral complex.

My main work as postdoc @plantophagy.bsky.social lab in @gmivienna.bsky.social is out in @natplants.nature.com 🌱🎉

We asked how can protein complexes diversify without compromising their function and explored this question using the plant #exocyst complex.

www.nature.com/articles/s41...

Congratulations Juan. Really amazing 🤩

Fair.
It is just easier for me to believe that someone tries to get away with something like this than someone actually getting away with it (for now at least). Mind boggling.

Whatever happened here cannot be called peer review imo. I don't know who did worse - the authors or the "reviewers". They even show the frickin map in a main figure.
Crazy that many excellent papers in Structure have to stand next to something like this.

Figure 1 from the preprint

Check out our preprint! With new molecular mechanisms, 140 subtomogram averages, and ~600 annotated cells under different conditions, we @embl.org were able to describe bacterial populations with in-cell #cryoET. And there’s a surprise at the end 🕵️

www.biorxiv.org/content/10.1...
#teamtomo