Expanded Interactome of the Intrinsically Disordered Protein Dss1

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Dss1 (Sem1) is a conserved, intrinsically disordered protein known for diverse functions.
• It participates in proteasome activity, DNA repair, transcription, and mRNA export.
• Dss1 is associated with complexes such as BRCA2, RPA, Csn12-Thp1, and TREX-2.

Purpose of the Study:

• To investigate the expanded interactome of Dss1 in Schizosaccharomyces pombe.
• To elucidate the role of Dss1's intrinsically disordered nature and transient structures in its interactions.
• To understand how Dss1's dynamic interactions influence cellular processes.

Main Methods:

• Proteomic analysis to identify Dss1 interacting partners.
• Biochemical assays to study protein-protein interactions.
• Genetic analysis in Schizosaccharomyces pombe to assess the functional consequences of Dss1 interactions.

Main Results:

• Dss1's interactome was expanded to include eIF3, the COP9 signalosome, and mitotic septins.
• A transiently populated C-terminal helix in Dss1 was identified, dynamically interacting with a central binding region.
• This helix interfered with ATP-citrate lyase interaction but was essential for septin binding.
• Loss of Dss1 reduced ATP-citrate lyase solubility and increased septin ring persistence.

Conclusions:

• Dss1's intrinsically disordered nature allows for dynamic interactions with multiple protein complexes.
• Transient structural elements within Dss1 are crucial for mediating specific protein interactions.
• These dynamic interactions enable Dss1 to modulate diverse cellular processes, including protein degradation, DNA repair, and cytoskeletal organization.