Intrinsically disordered proteins and liquid-liquid phase separation in SARS-CoV-2 interactomes

Area of Science:

• Virology
• Computational Biology
• Structural Biology

Background:

• Proteins play crucial roles in viral functions and host interactions.
• Understanding the structural properties of viral proteins, like disorder and connectivity, is key to deciphering viral mechanisms.
• The SARS-CoV-2 proteome's interactome properties, including protein disorder, are not fully understood.

Purpose of the Study:

• To investigate the relationship between protein disorder, connectivity, and phase separation in SARS-CoV-2 interactomes.
• To explore potential links between viral protein disorder and host-viral interactions within the human lung interactome.
• To compare the properties of viral protein interaction networks with those of eukaryotic systems.

Main Methods:

• Analysis of SARS-CoV-2 proteome subsets (membrane, nonstructural, full proteome).
• Evaluation of protein disorder, liquid-liquid phase separation (LLPS) probabilities, and node degrees in interaction networks.
• Integration of viral interactomes with human lung tissue interactome for host-viral interaction analysis.
• Correlation analysis to assess relationships between protein features and network properties.

Main Results:

• No clear correlation found between raw protein disorder and other features.
• A positive correlation observed between protein disorder and the mean disorder of its neighbors.
• Highly connected viral proteins (hubs) showed a tendency towards being more ordered compared to less connected proteins.
• Viral-host interactome analysis suggested potential links between new connections and protein disorder.

Conclusions:

• Viral protein interaction networks exhibit distinct properties compared to eukaryotic interactomes, particularly regarding protein disorder and hub connectivity.
• The findings suggest that viral hubs may be more structurally ordered, contrasting with previous observations in eukaryotic systems.
• Further research is warranted to explore these unique characteristics and their implications for viral pathogenesis and therapeutic strategies.