Sequence conservation of protein binding segments in intrinsically disordered regions

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• Intrinsically disordered proteins (IDPs) lack stable structures but contain functional regions.
• Protein-binding segments within IDRs, termed protean segments (ProSs), are crucial for biological processes.
• Sequence conservation in IDRs, including ProSs, is heterogeneous.

Purpose of the Study:

• To compare the sequence conservation of protean segments (ProSs) with structural domains (SDs) and other intrinsically disordered regions (non-ProSs).
• To understand the evolutionary patterns of ProSs and their functional constraints.

Main Methods:

• Utilized the IDEAL database to collect protean segments (ProSs).
• Compared sequence conservation scores across ProSs, structural domains (SDs), and non-ProSs.
• Analyzed conservation patterns of ProSs in human proteins across different species.

Main Results:

• Functionally constrained residues within ProSs are generally conserved.
• The conservation score distribution of ProSs resembles that of SDs, but not non-ProSs.
• ProSs in human proteins are primarily conserved within vertebrates.

Conclusions:

• Conservation patterns of ProSs align with those of structural domains, indicating functional constraints.
• Evolutionary dynamics of ProSs require consideration of evolutionary distance due to their potential for rapid emergence and loss.
• Further identification of ProSs may explain the observed heterogeneity in IDR sequence conservation.