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Reposted by Rasmus Hartmann-Petersen

Kresten Lindorff-Larsen @lindorfflarsen.bsky.social · 1d

The proteasome-substrate-shuttle protein UBQLN2 contains—like other quality control system proteins—a long region devoid of lysine (a lysine desert)

Martin Grønbæk-Thygesen (from @rhp-lab.bsky.social) et al show that introducing K here causes ubiquitylation and degradation

doi.org/10.1101/2025...

Fig. 1 – UBQLN2 is a conserved lysine-depleted protein. (A) Sequence comparison of
UBQLN2 orthologs in the indicated species. Intrinsically disordered regions in human
UBQLN2 based on MobiDB are shown as a blue bar. The domain organization based on the
SMART database is marked. Lysine residues are marked as black squares. (B) ESM-2
predictions of all possible single amino acid substitutions of human UBQLN2 presented as a
heat map. The wild-type residues are marked in blue. ESM-2 scores close to zero (light
yellow colors) indicate that the amino acid substitution is compatible with the ESM-2
language model, whereas negative scores (dark orange colors) indicate that the variant is
incompatible with the ESM-2 model. The domain organization (based on SMART) is aligned
above the map. Note that substitutions to lysine or cysteine in general appear detrimental, in
particular downstream of the UBL domain. (C) The AlphaFold2 predicted structured of
human UBQLN2 (AF-Q9UHD9-F1) (left panel). The UBL domain is colored blue, and the
UBA domain is colored orange and the STI1 regions green. Zoom in on the UBL domain
(right panel) with the lysine residues highlighted as stick representations and colored based
on the relative accessible surface area (rASA, dark red exposed; grey, buried).

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Reposted by Rasmus Hartmann-Petersen

Kresten Lindorff-Larsen @lindorfflarsen.bsky.social · 19d

Martin Grønbæk-Thygesen in @rhp-lab.bsky.social measured abundance and toxicity (both independently of function) of missense variants in aspartoacylase, and found that a subset of the low-abundance variants were toxic, induced a stress response which correlated with toxicity

doi.org/10.1038/s414...

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Reposted by Rasmus Hartmann-Petersen

Kresten Lindorff-Larsen @lindorfflarsen.bsky.social · 26d

I’m biased 🇩🇰, but this is quite nice to read:

I thought science hinged on prestige. Moving abroad made me reassess my priorities

www.science.org/content/arti...

I thought science hinged on prestige. Moving abroad made me reassess my priorities

In Denmark, this Ph.D. student fell in love with an egalitarian society that values work-life balance

www.science.org

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Reposted by Rasmus Hartmann-Petersen

PMC Protein Modules Community @pmc-modularity.bsky.social · Aug 15

We are back with an exciting seminar on September 8 at 3pm CEST! We’ll hear from Prof. Birthe Kragelund and Maximilian Vieler (@uu.se).

Register to attend:
tinyurl.com/PMCseminar2

Recordings of previous seminars: www.youtube.com/@PMCModularity

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Reposted by Rasmus Hartmann-Petersen

Eli Weinstein @eliweinstein.bsky.social · Jul 24

I'm looking for my first PhD student! We will push the frontiers of probabilistic machine learning for the molecular sciences, and study how to design new algorithms that exploit the unique properties of molecular systems to learn about the world.

efzu.fa.em2.oraclecloud.com/hcmUI/Candid...

PhD scholarship in Machine Learning for Molecules - DTU Chemistry

Advance large scale data generation for chemical and biological AI in a 3 year PhD. Work on the frontier of active learning, and develop novel probabilistic machine learning techniques for experiment ...

efzu.fa.em2.oraclecloud.com

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Reposted by Rasmus Hartmann-Petersen

Caroline Wright @carolinefwright.bsky.social · May 29

Both translational and fundamental curiosity-driven research are needed to fuel the incredible progress we're seeing in genomic medicine; an important message in this article and and some lovely quotes from @sarahlwynn.bsky.social
www.ft.com/content/25dd...

Curiosity underlies a breakthrough in rare disease

We must recognise and protect the pipelines that lead from research to real-world benefit

www.ft.com

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Reposted by Rasmus Hartmann-Petersen

Isabelle Zane @isabellease.bsky.social · May 23

@lindorfflarsen.bsky.social at #VariantEffect25

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Rasmus Hartmann-Petersen @rhp-lab.bsky.social · May 18

With the @lindorfflarsen.bsky.social group we present our map of degrons in all human transcription factors, incl. examples of constitutive degrons in exposed regions & buried degrons that are exposed upon mutation. In addition, we show that most TADs overlap with degrons. Work led by Fia Larsen.

Comprehensive degron mapping in human transcription factors

Gene expression is regulated by the targeted degradation of transcription factors through the ubiquitin-proteasome system. Transcription factors destined for degradation are recognized by E3 ubiquitin...

www.biorxiv.org

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Rasmus Hartmann-Petersen @rhp-lab.bsky.social · May 15

In collaboration with the @lindorfflarsen.bsky.social group we release our map of degrons in >5,000 human cytosolic proteins with >99% coverage. A machine learning model trained on the data identifies missense variants forming degrons in exposed & disordered regions. Work led by @vvouts.bsky.social.

A complete map of human cytosolic degrons and their relevance for disease

Degrons are short protein segments that target proteins for degradation via the ubiquitin-proteasome system and thus ensure timely removal of signaling proteins and clearance of misfolded proteins fro...

www.biorxiv.org

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Hemmo Meyer Lab @hemmo-lab.bsky.social · Apr 23

We are looking for a PhD student with interest in protein biochemistry on a really cool project “Cooperation of deubiquitinating enzymes and VCP/p97 in cellular stress responses”. Build your own reactions! fully funded. apply with code 193-25. #ubiquitin

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Reposted by Rasmus Hartmann-Petersen

Trends in Biochemical Sciences @cp-trendsbiochem.bsky.social · Mar 6

... wait! There's more great Review content!
☘️ mechanisms of #SAM homeostasis (Ben Tu et al)
☘️ glucose sensing by #glucokinase and how disease variants impact its function @sarahgersing.bsky.social @lindorfflarsen.bsky.social @rhp-lab.bsky.social

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Trends in Biochemical Sciences @cp-trendsbiochem.bsky.social · Jan 3

Now online - the Review "#Glucokinase: from allosteric glucose sensing to disease variants" from @sarahgersing.bsky.social, Torben Hansen, @lindorfflarsen.bsky.social, and @rhp-lab.bsky.social.

#GlucoseHomeostasis #GlucoseSensor #GCKMODY #CooperativeKinetics

authors.elsevier.com/a/1kN5M3S6Gf...

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Sarah Gersing @sarahgersing.bsky.social · Jan 2

Happy to share our review, 'Glucokinase: from allosteric glucose sensing to disease variants', published in @cp-trendsbiochem.bsky.social, which explores the fascinating enzyme glucokinase. authors.elsevier.com/a/1kN5M3S6Gf...

authors.elsevier.com

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Rasmus Hartmann-Petersen @rhp-lab.bsky.social · Dec 20

In our new paper we characterize the effects of indel variants on protein folding and stability using a new yeast-based protein folding sensor. The work was led by Sven Larsen-Ledet and supported by the @novo-nordisk.bsky.social.
Link to paper: www.cell.com/structure/fu...

Systematic characterization of indel variants using a yeast-based protein folding sensor

Larsen-Ledet et al. developed a yeast-based protein folding sensor to determine the effects of indel variants in DHFR. Using a saturated indel library, it was found that most indels are not tolerated. Several are temperature sensitive and folding is rescued by methotrexate. Rosetta and AlphaFold2 predictions correlate with the observed effects.

www.cell.com

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