Unusual arginine formations in protein function and assembly: rings, strings, and stacks

Area of Science:

• Structural Biology
• Biochemistry
• Protein Interactions

Background:

• Protein-protein interfaces often rely on key residues for stability.
• Arginine residues, known for forming ion pairs, can also interact through guanidinium pair interactions.
• Previous studies hinted at stable arginine-arginine interactions in solution.

Purpose of the Study:

• To investigate unusual arginine residue formations at protein-protein interfaces.
• To characterize the structural organization and stabilizing factors of arginine clusters.
• To understand the role of these clusters in protein oligomerization and function.

Main Methods:

• Analysis of over 70,000 protein structures and complexes.
• Utilized electron density data to confirm residue formations.
• Applied symmetry transformations to reconstruct complete protein assemblies.
• Examined C(ζ)-C(ζ) distances and hydrogen bonding networks.

Main Results:

• Identified clusters of 4-8 arginine residues at oligomeric protein interfaces, forming rings, stacks, and strings.
• Observed guanidinium groups stabilized by hydrogen bonds, water molecules, and counterions (in ~90% of cases).
• Documented planar stacking of guanidinium groups and involvement in multiple hydrogen bonds.

Conclusions:

• Arginine clusters can overcome electrostatic repulsion to form stable structures at protein interfaces.
• These clusters are strategically positioned for interaction with charged molecules, influencing protein assembly and function.
• The stability of arginine clusters is crucial for protein-protein oligomerization, molecular recognition, and ligand binding.