Distribution and complementarity of hydropathy in multisubunit proteins

Area of Science:

• Biochemistry
• Structural Biology
• Protein Interactions

Background:

• Understanding protein-protein interactions is crucial for deciphering biological processes.
• Quantifying the distribution of hydropathy (hydrophobicity/hydrophilicity) on protein surfaces provides insights into molecular recognition.

Purpose of the Study:

• To quantitatively analyze hydropathy distribution on protein surfaces.
• To introduce and validate a metric for 'hydropathy complementarity' between interacting protein surfaces.
• To explore the relationship between hydropathy complementarity and protein quaternary structure and dynamics.

Main Methods:

• Surveyed 40 multisubunit proteins and 2 protein-protein complexes.
• Assayed hydropathy distribution on exterior, interior, contact, and noncontact surfaces of isolated subunits.
• Developed and applied a 'hydropathy complementarity' function to quantify matching hydropathy patterns.

Main Results:

• The difference in hydropathy between protein interior and exterior is relatively constant.
• Contact surfaces are generally more hydrophobic than exterior surfaces, but vary among proteins.
• Protein interfaces show significant hydropathy complementarity, indicating matching hydrophobic and hydrophilic regions.
• High hydropathy complementarity correlates with static, inflexible protein interactions.

Conclusions:

• Hydropathy complementarity is a valuable tool for predicting protein docking and specificity.
• Complementary hydropathy patterns drive specific protein-protein recognition.
• Hydrophilically driven interactions can be associated with dynamic quaternary organization and allostery.