Pervasive, conserved secondary structure in highly charged protein regions

Area of Science:

• Molecular Biology
• Structural Biology
• Biophysics

Background:

• Protein function is dictated by sequence, but understanding this link is challenging.
• Structure-based and disorder-based approaches are typically studied separately.
• Highly charged protein regions are generally presumed to be intrinsically disordered.

Approach:

• Utilized advanced structure prediction and experimental data.
• Analyzed protein regions with >40% charged residues.
• Developed a composition-based classifier to predict structure.

Key Points:

• Approximately 40% of highly charged regions form well-structured helices.
• Common disorder predictors (high charge, low hydrophobicity) are compatible with helical structures.
• A simple composition classifier outperforms traditional heuristics for structure prediction.

Conclusions:

• Helical structures are more common in charged regions than previously thought.
• Findings necessitate integrating structure and disorder perspectives.
• Characterized the conservation of these helical structures across diverse proteomes.