Intrinsic disorder in protein interactions: insights from a comprehensive structural analysis.

Area of Science:

• Biochemistry
• Structural Biology
• Bioinformatics

Background:

• Intrinsically disordered regions (IDRs) are crucial for protein function but their role in protein complexes is less understood.
• Conventional views suggest coupled folding and binding, but the extent of disorder in complexes requires further investigation.

Purpose of the Study:

• To investigate the prevalence and characteristics of intrinsically disordered regions in a large set of protein complexes.
• To explore the disorder-to-order transitions upon complex formation and their localization.
• To compare disorder levels in homodimers versus heterodimers and elucidate regulatory mechanisms.

Main Methods:

• Large-scale analysis of intrinsically disordered regions using a non-redundant dataset of hundreds of protein complexes.
• Examination of disorder-to-order transitions at binding interfaces.
• Comparative analysis of disorder in homodimers and heterodimers.

Main Results:

• A significant fraction of residues in protein complexes are intrinsically disordered (up to one-third).
• Disorder-to-order transitions frequently occur upon complex formation, often at binding interfaces.
• Homodimers, particularly symmetrical ones, show significantly higher disorder than heterodimers.

Conclusions:

• Intrinsically disordered regions play a substantial role in protein complexes, with disorder-to-order transitions being a common feature.
• Disordered regions in complexes are important for regulating binding specificity, similar to their role in monomeric proteins.
• The diversity of roles for IDRs in various protein oligomeric forms warrants further research.