The disordered PCI-binding human proteins CSNAP and DSS1 have diverged in structure and function

Area of Science:

• Protein biochemistry
• Molecular biology
• Structural biology

Background:

• Intrinsically disordered proteins (IDPs) are crucial components of large protein assemblies.
• DSS1 and CSNAP are small, acidic IDPs associated with PCI complexes like the proteasome lid and COP9 signalosome.
• Previous studies suggested similar structures and functions for DSS1 and CSNAP, but with differing interactome sizes.

Purpose of the Study:

• To characterize the residue-level structural properties of human DSS1 and CSNAP.
• To investigate the ubiquitin-binding propensities of DSS1 and CSNAP.
• To elucidate the structural and functional divergence between DSS1 and CSNAP.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to analyze protein structures.
• Comparative analysis of structural features at the residue level was performed.
• Ubiquitin binding assays were conducted to assess protein interactions.

Main Results:

• DSS1 and CSNAP exhibit unique structural features absent in the other protein.
• CSNAP demonstrates a lack of significant ubiquitin binding, contrasting with DSS1.
• The findings reveal substantial divergence in both structure and function between DSS1 and CSNAP.

Conclusions:

• DSS1 and CSNAP have evolved distinct structural and functional characteristics.
• Subtle sequence variations in IDPs can lead to significant differences in functional traits and interaction capabilities.
• These differences contribute to their varied roles within cellular complexes and impact interactome sizes.