Structural Descriptors for Subunit Interface Regions in Homodimers: Effect of Lipid Membrane and Secondary Structure...

Area of Science:

• Structural Biology
• Biochemistry
• Computational Biology

Background:

• Understanding protein-protein interactions is crucial for deciphering biological processes.
• Homodimer interfaces exhibit diverse structural characteristics influenced by cellular location and secondary structure.

Purpose of the Study:

• To analyze and compare the structural features of homodimer interfaces versus non-interface surfaces.
• To investigate the impact of lipid environment and secondary structure type on interface properties.

Main Methods:

• Analysis of 1311 homodimers across cytoplasmic alpha-helix, cytoplasmic beta-strand, and membrane complex categories.
• Evaluation of residue attributes: solvent-accessible surface area (SASA), protrusion index, surface planarity, and surface roughness.
• Comparison of interface and surface residue distributions and contact pair frequencies.

Main Results:

• Interface rims showed higher SASA and protrusion index than the rest of the surface.
• Membrane complex residues protruded less due to hydrophobic environments, reducing interface-surface distinction.
• Surface roughness and planarity were significantly higher at interfaces, particularly in cytoplasmic complexes, favoring monomer association.

Conclusions:

• Rugged and planar surfaces at homodimer interfaces promote association via van der Waals and hydrogen bonding.
• Interface characteristics vary between cytoplasmic and membrane proteins, with hydrophobic interactions dominating in lipid environments.
• Polar residue contacts, though less frequent, are more likely than hydrophobic contacts at interfaces.