Jess Niblo (@jessniblo) Bsky

Huge thanks to my co-first author Nirbhik Acharya, whose NMR data was essential to validating these predictions, Maxwell Watkins, and our PIs @shaharsu.bsky.social and @castanedalab.bsky.social!

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Despite sequence variability, these hotspots and key functional motifs are conserved! We propose intramolecular IDR:folded domain contacts bury these motifs to keep the protein in a less-active closed state. When disrupted, the ensemble expands, exposing these motifs and enhancing activity.

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Using CALVADOS coarse-grained simulations (thanks @lindorfflarsen.bsky.social), I mapped how IDRs interact with their central folded domains, which matched NMR data. We found distinct interaction “hotspots” within the IDRs, which help stabilize a closed state where binding sites are less accessible.

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Intramolecular interactions between folded and disordered regions shape ubiquilin structure and function Multidomain proteins consist of folded domains connected by intrinsically disordered regions. The flexibility afforded by the disordered regions coupled to the structure and surface chemistry of folded regions allows for unique structural and functional features in these proteins. Yet how intramolecular interactions between disordered regions and folded domains affect multidomain protein structure and function remain poorly understood. Here we use a range of biophysical and computational approaches to measure the intramolecular interactions between the folded domains and disordered regions of ubiquilins (UBQLNs) - essential components of protein quality control that shuttle poly-ubiquitinated client proteins to proteasomal degradation or autophagy. Starting with the yeast UBQLN homolog Dsk2, we find that interactions between two folded domains located at the opposite ends of UBQLN bring about a closed conformation. The prevalence of this closed conformation, however, is modulated by intramolecular interactions involving the disordered regions and folded STI1 domain at the center of the protein. Simulations and analysis of UBQLN homologs across multiple eukaryotic lineages reveals that these disordered:folded domain interactions exist in some UBQLN homologs but are absent in others, indicating possible fundamental differences in function among proteins with the same multidomain architecture. ### Competing Interest Statement The authors have declared no competing interest.

Ever wonder how IDRs and folded domains work together to control function? Using ubiquilins, multidomain proteins involved in protein degradation, we show in our new preprint that IDRs aren’t just linkers, but regulate ensemble and function. Read it here: doi.org/10.64898/202...

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STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation - The EMBO Journal Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing condensates via multivalent interactions wit...

Yeast ubiquilin Dsk2 scaffolds proteasome-containing condensates under stress via multivalent interactions – @castanedalab.bsky.social et al show how dynamic interactions among its STI1 domain & transient helices in its disordered region promote its phase-separation
link.springer.com/article/10.1...

2 months ago 22 16 0 1

So happy to announce our new preprint, “A geothermal amoeba sets a new upper temperature limit for eukaryotes.” We cultured a novel amoeba from Lassen Volcanic NP (CA, USA) that divides at 63°C (145°F) 🔥 - a new record for euk growth!
#protistsonsky 🧵

4 months ago 496 165 16 32

The power of collaborations! With @shaharsu.bsky.social, his PD @jessniblo.bsky.social and CALVADOS3 (thanks to @lindorfflarsen.bsky.social ) we show how STI1 (red) may engage with sequences that match transient helices within IDRs of Ub-binding shuttle protein Dsk2 www.biorxiv.org/content/10.1...

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Posts by Jess Niblo