Sarah Gersing

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...

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.

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...

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.

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...

In our newest preprint we map degrons for >5,000 cytosolic proteins and we develop a degron predictor that can predict novel degron formation, a potential mechanism of pathogenicity. Many thanks to @rhp-lab.bsky.social, @lindorfflarsen.bsky.social and @dougfowler.bsky.social for their supervision.

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...

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.

Do you think that cooperativity requires more than one binding site or subunit? Or just want to read about an interesting enzyme for which both gain- and loss-of-function variants can cause metabolic disease?

Then check out @sarahgersing.bsky.social's review on glucokinase: doi.org/10.1016/j.ti...

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...

Many thanks to @rhp-lab.bsky.social, @lindorfflarsen.bsky.social and Torben Hansen for the collaboration, and to the editor and reviewers for their constructive feedback.

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...

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.

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...