Interactions by Disorder - A Matter of Context.

Area of Science:

• Biochemistry and Molecular Biology
• Structural Biology
• Systems Biology

Background:

• Protein interactions form complex networks essential for life.
• Recent advances allow studying protein interactions with greater precision.
• Intrinsically disordered proteins (IDPs) and their roles are increasingly recognized.

Purpose of the Study:

• To explore protein-protein interactions beyond direct physical contact.
• To emphasize the role of structural disorder and flanking regions in protein interactions.
• To highlight the regulatory potential of molecular context in biological processes.

Main Methods:

• Review of existing literature and selected examples.
• Discussion of physicochemical, biomolecular, and physiological contexts.
• Analysis of IDPs and their short linear motifs.

Main Results:

• Disorder-based interactions, including flanking regions, offer significant regulatory potential.
• Multivalency, charge clusters, hydrophobic patches, and dynamics modulate binding.
• Contextual factors influence allosteric regulation, cooperativity, and feedback mechanisms.

Conclusions:

• The molecular context and flanking regions of disordered proteins are crucial for understanding interaction potential.
• This understanding unlocks new avenues for energetic modulation in biological processes.
• Insights are relevant for drug discovery and development targeting protein interactions.