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Rasmus Hartmann-Petersen

@rhp-lab.bsky.social

Professor at the Linderstrøm-Lang Centre for Protein Science, University of Copenhagen. Interests: Protein Quality Control, Genetics, Molecular Chaperones, Degrons.

6 Posts420 Follower402 Folgt
Kresten Lindorff-Larsen@lindorfflarsen.bsky.social · 6mo ago

Happy to share our newest preprint on Parkin missense variants in work led by Erna Sol & @vvouts.bsky.social in @rhp-lab.bsky.social Using a multiplexed assay we determined the effects of 9,212 out of 9,300 single amino acid substitutions and nonsense Parkin variants. 1/n doi.org/10.64898/202...

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bioRxiv Genetics@biorxiv-genetic.bsky.social · 6mo ago

Comprehensive Variant Effect Map of Parkin-Mediated Mitophagy in Parkinson's Disease https://www.biorxiv.org/content/10.64898/2026.02.09.704749v1

Rasmus Hartmann-Petersen@rhp-lab.bsky.social · 6mo ago

We map the effects of >99% Parkin (PRKN) missense variants on mitophagy. The landscape separates benign & pathogenic variants, reveals misfolded variants induce mitophagy and flags hypomorphic alleles for rescue. Collab w. @lindorfflarsen.bsky.social. Work led by Erna Sol & @vvouts.bsky.social.

bioRxiv Genetics@biorxiv-genetic.bsky.social · 6mo ago

Comprehensive Variant Effect Map of Parkin-Mediated Mitophagy in Parkinson's Disease https://www.biorxiv.org/content/10.64898/2026.02.09.704749v1

Rasmus Hartmann-Petersen@rhp-lab.bsky.social · 6mo ago

Now on bioRxiv: genome‑wide CRISPR KO reveals BAG6 (chaperone) and RNF126 (E3) as core PQC for non‑native missense proteins. VAMP seq. shows >1000 Parkin variants are BAG6 targets, including known pathogenic variants. Work led by Line Pedersen. Collab with @lindorfflarsen.bsky.social

bioRxiv Biochemistry@biorxiv-biochem.bsky.social · 6mo ago

BAG6 and RNF126 are broadly involved in protein quality control of non-native missense protein variants https://www.biorxiv.org/content/10.64898/2026.02.04.703735v1

Kresten Lindorff-Larsen@lindorfflarsen.bsky.social · 7mo ago

Second preprint of the year in which @sarahgersing.bsky.social from @rhp-lab.bsky.social mapped the effects of >7500 variants in glucokinase (GCK) on the interaction with the glucokinase regulatory protein so that we now have a 3D GCK scan (abundance, interaction, activity) doi.org/10.64898/202...

Figure 2 from the paper with: (A) Heatmap showing the interaction score of each possible amino acid substitution along the GCK sequence. (B) Interaction score distributions of missense, synonymous and nonsense variants. (C) The median interaction score of each GCK residue mapped onto the structure of the GCK–GKRP complex.
Rasmus Hartmann-Petersen@rhp-lab.bsky.social · 7mo ago

New preprint! Led by @sarahgersing.bsky.social we map how 7,500+ variants in glucokinase (GCK) affect binding to GKRP and disentangle this from stability. We now have activity, abundance, and interaction scores for 7,128 GCK variants - a resource for understanding phenotypes and glucose homeostasis.

Rasmus Hartmann-Petersen@rhp-lab.bsky.social · 7mo ago

New preprint! Led by @sarahgersing.bsky.social we map how 7,500+ variants in glucokinase (GCK) affect binding to GKRP and disentangle this from stability. We now have activity, abundance, and interaction scores for 7,128 GCK variants - a resource for understanding phenotypes and glucose homeostasis.

bioRxiv Biochemistry@biorxiv-biochem.bsky.social · 7mo ago

Mapping the GCK-GKRP interaction landscape using deep mutational scanning by reverse two-hybrid screening https://www.biorxiv.org/content/10.64898/2026.01.15.699699v1

Kresten Lindorff-Larsen@lindorfflarsen.bsky.social · 10mo ago

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).
bioRxivpreprint@biorxivpreprint.bsky.social · 10mo ago

The importance of UBQLN2 ubiquitylation for its turnover and localization https://www.biorxiv.org/content/10.1101/2025.10.02.679934v1

Eli Weinstein@eliweinstein.bsky.social · last yr.

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

Rasmus Hartmann-Petersen@rhp-lab.bsky.social · last yr.

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...

biorxiv.org

Rasmus Hartmann-Petersen@rhp-lab.bsky.social · last yr.

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...

biorxiv.org

Hemmo Meyer Lab@hemmo-lab.bsky.social · last yr.

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

Rasmus Hartmann-Petersen@rhp-lab.bsky.social · 2y ago

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.

cell.com