Why do eukaryotic proteins contain more intrinsically disordered regions?

Area of Science:

• Biochemistry
• Molecular Biology
• Bioinformatics

Background:

• Intrinsic disorder is more prevalent in eukaryotic proteins compared to prokaryotic ones.
• Protein disorder prediction methods rely on amino acid sequences, suggesting sequence differences underlie disorder variations.
• Eukaryotic and prokaryotic proteins show distinct sequence compositions, particularly in regions connecting functional domains.

Purpose of the Study:

• To investigate the sequence-based differences responsible for the higher intrinsic disorder in eukaryotic proteins versus prokaryotic proteins.
• To identify specific protein regions and amino acid compositions contributing to these disorder variations.
• To explore the evolutionary implications of amino acid frequency changes in protein disorder.

Main Methods:

• Comparative proteome analysis of eukaryotic and prokaryotic organisms.
• Identification and characterization of linker regions connecting Pfam domains.
• Amino acid composition analysis focusing on serine, proline, and isoleucine frequencies.
• Assessment of intrinsic disorder levels in different protein regions.

Main Results:

• Eukaryotic proteins possess longer linker regions compared to prokaryotic proteins.
• Eukaryotic linker regions are significantly more disordered (38%) than prokaryotic ones (12-16%).
• Increased disorder in eukaryotes is linked to higher frequencies of serine (8.6% vs. 6.5%) and proline (5.4% vs. 4.0%), and lower isoleucine (5.3% vs. ~7.5%).

Conclusions:

• The difference in intrinsic disorder between eukaryotic and prokaryotic proteins originates mainly from their linker regions.
• Specific amino acid frequency variations, particularly in serine, proline, and isoleucine, are key drivers of increased disorder in eukaryotic linkers.
• The findings raise questions about the causal relationship between amino acid composition and disorder in protein linkers.