This study examines the mechanisms by which cell division and chromatin remodelling facilitate identity transitions during root tip regeneration. We show that histone deacetylases (HDACs) act early in...

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.

Single-molecule tracking of transcription factors in living cells revealed how mutations that make short activation domains stronger increased the fraction of transcription factor molecules bound to c...

Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing condensates via multivalent interactions wit...

Transcription factors regulate gene expression with DNA-binding domains (DBDs) and activation domains. It is generally assumed that DBDs are solely responsible for interacting with DNA and chromatin. ...

Transcription factor proteins bind to specific DNA promoter sequences and initiate gene transcription. These proteins often contain intrinsically disordered activation domains (ADs) that regulate their transcriptional activity. Like other disordered protein regions, ADs do not have a fixed three-dimensional structure and instead exist in an ensemble of conformations. Disordered ensembles contain sequence-encoded structural preferences which are often linked to their function. We hypothesize this link exists between the structural preferences of AD ensembles and their ability to induce gene expression.