STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation

ABSTRACT: Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing condensates via multivalent interactions with proteasomes and polyubiquitinated substrates under stress conditions. Here, we identify the chaperone-binding STI1 domain as the main driver of Dsk2 self-association and phase separation. Using nuclear magnetic resonance (NMR) spectroscopy and computational simulations, we find that the STI1 domain interacts with three transient amphipathic helices within the intrinsically-disordered regions of Dsk2. Removal of either the STI1 domain or these helices significantly reduces Dsk2's propensity to form condensates. In vivo, perturbing STI1-helix interactions, specifically removal of the transient

SUBMITTER: Nirbhik Acharya 

PROVIDER: S-SCDT-10_1038-S44318-026-00696-1 | biostudies-other |

REPOSITORIES: biostudies-other