Morphology of protein-protein interfaces

Area of Science:

• Protein structure and function
• Biochemistry
• Structural biology

Background:

• Soluble proteins often function as oligomers.
• Previous studies highlighted hydrophobicity and complementarity in protein interface stability.
• Averaging structural features over diverse interfaces obscures individual interface stabilization mechanisms.

Purpose of the Study:

• To visually survey protein-protein interaction surfaces in homodimeric proteins.
• To identify and characterize the structural features stabilizing these interfaces.

Main Methods:

• Visual survey of 136 homodimeric proteins from the Brookhaven Protein Data Bank.
• Analysis of protein-protein interaction surfaces, focusing on hydrophilicity patterns and structural features.

Main Results:

• Most interfaces are between globular subunits.
• Interface hydrophilicity is highly variable.
• Only one-third of interfaces have a distinct hydrophobic core; the rest show mixed hydrophobic/hydrophilic patterns and water molecules.
• Intertwined interfaces are highly hydrophobic and associated with stability and symmetry.

Conclusions:

• The classic hydrophobic core model applies to a minority of homodimeric protein interfaces.
• Most homodimeric proteins utilize a combination of small hydrophobic patches, polar interactions, and bridging water molecules for stability.
• Interface structure, specifically the presence of a hydrophobic core, does not correlate with protein function.