Expanded Interactome of the Intrinsically Disordered Protein Dss1

Abstract

Summary: Dss1 (also known as Sem1) is a conserved, intrinsically disordered protein with a remarkably broad functional diversity. It is a proteasome subunit but also associates with the BRCA2, RPA, Csn12-Thp1, and TREX-2 complexes. Accordingly, Dss1 functions in protein degradation, DNA repair, transcription, and mRNA export. Here in Schizosaccharomyces pombe, we expand its interactome further to include eIF3, the COP9 signalosome, and the mitotic septins. Within its intrinsically disordered ensemble, Dss1 forms a transiently populated C-terminal helix that dynamically interacts with and shields a central binding region. The helix interfered with the interaction to ATP-citrate lyase but was required for septin binding, and in strains lacking Dss1, ATP-citrate lyase solubility was reduced and septin rings were more persistent. Thus, even weak, transient interactions within Dss1 may dynamically rewire its interactome. : Schenstrøm et al. demonstrate that the disordered protein Dss1 forms a transient intramolecular interaction between the C-terminal helical region and a central hydrophobic region. Proteomics reveal several Dss1-binding proteins, including all PCI-domain protein complexes. The dynamic fold-back structure regulates Dss1 interactions with the mitotic septins and ATP-citrate lyase. Keywords: intrinsically disordered proteins, protein degradation, proteasome, PCI domain