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maltegersch.bsky.social
Malte Gersch
@maltegersch.bsky.social
860 followers 300 following 17 posts
Chemical Biologist & Research Groupleader at Max Planck & TU Dortmund. Interested in DUBs, proteases, ubiquitin, the outdoors and more. Views are my own. cgc.mpg.de/gersch
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maltegersch.bsky.social
Malte Gersch @maltegersch.bsky.social · May 5
Super happy to share that our work on the specific inhibition of USP30 - a clinical stage Parkinson's drug target - is now online at NSMB www.nature.com/articles/s41... Have a read if you fancy chimeric protein engineering or a framework for DUB ligandability. Huge congratulations to Nafizul & team!
Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30 - Nature Structural & Molecular Biology
Kazi et al. report the crystal structure of the mitochondrial deubiquitinase USP, a clinical stage Parkinson’s disease drug target, in complex with a specific inhibitor. The authors delineate a framew...
www.nature.com
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Reposted by Malte Gersch
kranzuschlab.bsky.social
Kranzusch Lab @kranzuschlab.bsky.social · 19d
You’ve heard of ubiquitination, meet deazaguanylation: Doug Wassarman in our lab discovered phage defense pathways have co-opted Q nucleobase biosynthetic enzymes to catalyze a new form of protein conjugation chemistry @science.org

www.science.org/doi/10.1126/...
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Reposted by Malte Gersch
sonjalorenzlab.bsky.social
Lorenz Lab @sonjalorenzlab.bsky.social · 21d
Allosteric activation of a ubiquitin ligase by an internal kinase domain! Congratulations to our team member Thornton Fokkens for this fascinating discovery in a neglected disease area with strong therapeutic need. Many thanks to all our great collaborators!
www.sciencedirect.com/science/arti...
A Leishmania virulence factor harnesses an allosteric kinase switch to regulate its ubiquitin ligase activity
Stringent control of ubiquitylation is a central requirement of signaling specificity in eukaryotes. Here, we discover a domain module integrating pro…
www.sciencedirect.com
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Reposted by Malte Gersch
frisophagy.bsky.social
Michele Frison @frisophagy.bsky.social · 5d
How can mitophagy be an effective quality control mechanism if mtDNA mutations reach high enough levels to cause disease?

This question led us into a dark path, full of concepts of evolutionary genetics, germline stem cell biology and mito-nuclear compatibility.

www.science.org/doi/10.1126/...
Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations
Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...
www.science.org
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Reposted by Malte Gersch
johanneszuber.bsky.social
Johannes Zuber @johanneszuber.bsky.social · 5d
Just out in @science.org: Together with the lab of @wilhelmpalm.bsky.social, we used sequential in-vitro/in-vivo CRISPR screens to decipher metabolic adaptations in tumors. We find that acidosis is a dominant factor that shapes energy metabolism and stress resilience. www.science.org/doi/10.1126/...
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Reposted by Malte Gersch
pedrobeltrao.bsky.social
Pedro Beltrao @pedrobeltrao.bsky.social · 6d
new preprint: Ubiquitin is a protein modification linked with degradation but known to regulate other functions. Over 100k ubiquitination sites have been discovered and here we (@julianvangerwen.bsky.social + others) try to prioritize those most critical to the cell www.biorxiv.org/content/10.1...
The functional landscape of the human ubiquitinome
Protein ubiquitination regulates cell biology through diverse avenues, from quality control-linked protein degradation to signaling functions such as modulating protein-protein interactions and enzyme...
www.biorxiv.org
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Reposted by Malte Gersch
mtrost.bsky.social
Matthias Trost @mtrost.bsky.social · 22d
Are you using DIA mass spectrometry in proteomics?

We have just put this paper online: www.biorxiv.org/content/10.1...

Here, we came up with some Recommendations for Quantitative Data-Independent Acquisition (DIA) Proteomics using Controlled Quantitative Experiments (CQEs)

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Recommendations for Quantitative Data-Independent Acquisition (DIA) Proteomics using Controlled Quantitative Experiments (CQEs)
Advances in mass spectrometry and associated computational tools have resulted in the wide-spread adoption of Data-Independent Acquisition (DIA) for proteomics. Experiments using state-of-the-art inst...
eur03.safelinks.protection.outlook.com
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Reposted by Malte Gersch
natchembio.nature.com
Nature Chemical Biology @natchembio.nature.com · Aug 21
A new paper reports direct ubiquitination of a small molecule BRD1732 in cells. BR31732 ubiquitination is E3 ligase-dependent and leads to inhibition of proteasomal degradation.

www.nature.com/articles/s41...
Highly specific intracellular ubiquitination of a small molecule - Nature Chemical Biology
Li et al. discovered that the cytotoxic synthetic small molecule BRD1732 is directly ubiquitinated in cells. Ubiquitination of BRD1732 is E3 ligase dependent and leads to inhibition of proteasomal deg...
www.nature.com
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Reposted by Malte Gersch
nature.com
Nature @nature.com · Aug 28
For life to emerge on Earth, peptides must first have formed without the aid of enzymes — but how? Reactions of sulfur-containing molecules might have been key

go.nature.com/4oX04jC
Origins of life: the molecules that could have unlocked peptide synthesis
For life to emerge on Earth, peptides must first have formed without the aid of enzymes — but how? Reactions of sulfur-containing molecules might have been key.
go.nature.com
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Reposted by Malte Gersch
sonjalorenzlab.bsky.social
Lorenz Lab @sonjalorenzlab.bsky.social · Sep 2
Delighted to share our work on cellular ubiquitination of drug-like compounds by HUWE1 - a surprising journey! Kudos to all contributors & first authors, Barbara Orth and Pavel Pohl. Sincere thanks to @ireserra.bsky.social ‬ #NatCommun for expertly guiding the winding publishing path.
rdcu.be/eDzPk
Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1
Nature Communications - Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule...
rdcu.be
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Reposted by Malte Gersch
pastelbio.bsky.social
PastelBio @pastelbio.bsky.social · Sep 13
Fully‐Functionalized Natural Product Probes to Expand the Chemical Tractability of the Human Proteome onlinelibrary.wiley....

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#proteomics #prot-paper
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Reposted by Malte Gersch
olibclarke.bsky.social
Oli Clarke @olibclarke.bsky.social · Sep 13
This one is a bit of a departure from the usual and definitely a work in progress!

We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.

Read on for details... 1/x
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Reposted by Malte Gersch
andrea-musacchio.bsky.social
Andrea Musacchio @andrea-musacchio.bsky.social · Sep 15
The BUB1 and BUBR1 paralogs scaffold the kinetochore fibrous corona | Science Advances www.science.org/doi/10.1126/...

Congratulations @vcmentowski.bsky.social for solving a remarkably challenging molecular puzzle
The BUB1 and BUBR1 paralogs scaffold the kinetochore fibrous corona
The kinetochore fibrous corona docks on CENP-E and a second elusive receptor identified as the checkpoint protein BUB1.
www.science.org
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Reposted by Malte Gersch
frezzalab.bsky.social
Christian Frezza @frezzalab.bsky.social · 28d
Covariation MS uncovers a protein that controls cysteine catabolism

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

Beautiful work from Ed Chouchani!
Covariation MS uncovers a protein that controls cysteine catabolism - Nature
A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.
www.nature.com
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Reposted by Malte Gersch
natbiotech.nature.com
Nature Biotechnology @natbiotech.nature.com · Sep 4
Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes - @helmholtz-hiri.bsky.social go.nature.com/4n7zDpG
Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes - Nature Biotechnology
Append editing of ADP-ribosyl to thymine is used for precise modifications in bacteria and eukaryotes.
go.nature.com
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Reposted by Malte Gersch
hillerlab.bsky.social
HillerLab @hillerlab.bsky.social · Aug 11
New paper alert! Stellar work by brilliant lead first author @annaleder.bsky.social together with project leader @masgu.bsky.social reveals a groundbreaking discovery: PDIA6 forms multi-chaperone condensates creating "folding factories" in the ER. www.nature.com/articles/s41...
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Reposted by Malte Gersch
fleurmferguson.bsky.social
Fleur Ferguson @fleurmferguson.bsky.social · Aug 11
Excited to share our latest work developing molecular glue degraders of ZBTB11, now out in @natchembio.nature.com
www.nature.com/articles/s41...
ZBTB11 depletion targets metabolic vulnerabilities in KRAS inhibitor-resistant PDAC - Nature Chemical Biology
Depletion of a transcriptional factor ZBTB11 using molecular glue degraders can overcome oxidative-phosphorylation-mediated KRAS inhibitor resistance in pancreatic ductal adenocarcinoma with low acute...
www.nature.com
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Reposted by Malte Gersch
amyweeks.bsky.social
Amy Weeks @amyweeks.bsky.social · Jul 18
Excited to share our latest: we engineered the reactivity of a bacterial E1-like enzyme for ATP-driven modification of C termini. Our tool mimics the logic of peptide bond formation in biology for precision modification of proteins in vitro. 🧪https://rdcu.be/ewN7C
Engineered reactivity of a bacterial E1-like enzyme enables ATP-driven modification of protein and peptide C termini
Nature Chemistry - In living systems, ATP provides an energetic driving force for protein synthesis and modification. Now, an engineered enzymatic tool has been developed for high-yield, ATP-driven...
rdcu.be
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Reposted by Malte Gersch
uwmadisonrna.bsky.social
Aaron and the Hoskins Lab at UW Madison @uwmadisonrna.bsky.social · Jul 30
This has a neat mechanism of inhibition:
www.nature.com/articles/s41...
SuFEx-based antitubercular compound irreversibly inhibits Pks13 - Nature
A preclinical covalent compound, CMX410, contains a aryl fluorosulfate warhead that targets the acyltransferase domain of Mtb Pks13, an essential enzyme in cell-wall biosynthesis, making it a pro...
www.nature.com
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Reposted by Malte Gersch
science.org
Science Magazine @science.org · Jul 31
This week in Science, researchers report an artificial molecular motor that can twist a molecular thread to form a mechanically interlocked molecule. The approach creates opportunities to fabricate mechanically interlocked molecules with precise structural control.

Learn more: scim.ag/40FboGP
This illustration shows consecutive stages during operation of a molecular catenating machine.
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Reposted by Malte Gersch
pinkigahlot.bsky.social
Pinki Gahlot @pinkigahlot.bsky.social · Aug 1
Thrilled to share our work on the role of Ataxin-3 in lysosome regeneration published in @embojournal.org . Here we show that Atxn3 targets K48-K63 branched ubiquitin chains on damaged lysosomes and mediates restoration of lysosomal function via microautophagy.

www.embopress.org/doi/full/10....
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Reposted by Malte Gersch
jamesnathanlab.bsky.social
James Nathan @jamesnathanlab.bsky.social · Jul 15
Delighted to share our latest work on ABHD11 as a novel deglutarylating enzyme, and its role in T cell metabolism @natchembio.nature.com rdcu.be/ewiYZ. Many congratulations to co-first authors Guine Grice, Eleanor Minogue and @hudsonwilco.bsky.social! Great team effort with Randall Johnson's lab.
Lipoyl deglutarylation by ABHD11 regulates mitochondrial and T cell metabolism
Nature Chemical Biology - Glutarate rewires cell metabolism through conjugation to proteins or fatty acids, but how glutarylation is regulated is unclear. ABHD11 was identified as a...
rdcu.be
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Reposted by Malte Gersch
hellerschmiedlab.bsky.social
Hellerschmied Lab @hellerschmiedlab.bsky.social · Jul 15
Very happy to see our contribution to a better understanding of Hsp70/90 #chaperones online! Congrats and a big thank you to all co-authors, collaborators and reviewers! #proteostasis @poepsel-lab.bsky.social @crc1430.bsky.social @unidue-zmb.bsky.social
natsmb.nature.com
Nature Structural & Molecular Biology @natsmb.nature.com · Jul 14
New online: Conformational plasticity of a BiP–GRP94 chaperone complex
Conformational plasticity of a BiP–GRP94 chaperone complex
Nature Structural & Molecular Biology, Published online: 14 July 2025; doi:10.1038/s41594-025-01619-0BiP–glucose-regulated protein 94 chaperones are critical to the proper folding of secretory and transmembrane proteins. Brenner et al. provide biochemical and structural insight into a conserved mechanism of chaperone cooperation underlying this quality control process.
go.nature.com
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Reposted by Malte Gersch
mads100tist.bsky.social
MwahahahahahadScientist @mads100tist.bsky.social · Jun 29
These NPG spinoff journals are out of control
A picture of a bottle of hummus. It is labeled NATURE HUMMUS
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Reposted by Malte Gersch
nikolasklink.bsky.social
Niko Klink @nikolasklink.bsky.social · Jul 5
Really excited to share the first chapter of my PhD as a preprint titled: Targeted degradation of USP7 in solid cancer cells reveals disparate effects of deubiquitinase inhibition vs. acute protein depletion: www.biorxiv.org/content/10.1.... If that sounds interesting to you, small tweetorial below👇
Targeted degradation of USP7 in solid cancer cells reveals disparate effects of deubiquitinase inhibition vs. acute protein depletion
Proteolysis-targeting chimeras (PROTACs) co-op the ubiquitin system for targeted protein degradation, creating opportunities to interrogate cellular functions of proteins through "chemical knockdown"....
www.biorxiv.org
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Reposted by Malte Gersch
stephanhammer.bsky.social
Stephan Hammer @stephanhammer.bsky.social · Jul 11
Regioselective azole alkylation at gram scale and in late-stage settings now in @angewandtechemie.bsky.social, enabled by engineered enzymes.

onlinelibrary.wiley.com/doi/10.1002/...
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