Experimentally determined hydrophobicity scale for proteins at membrane interfaces

Area of Science:

• Biophysics
• Biochemistry
• Membrane Biology

Background:

• Membrane-active oligopeptides partition into lipid interfaces, influencing secondary structure formation.
• Understanding membrane protein folding and insertion requires a quantitative free energy scale for peptide partitioning.
• Existing hydrophobicity scales may not fully account for peptide bond contributions at membrane interfaces.

Purpose of the Study:

• To determine a complete interfacial hydrophobicity scale including the peptide bond.
• To quantitatively describe the coupling between structure formation and partitioning of peptides into membrane interfaces.
• To provide a basis for understanding membrane protein folding and insertion.

Main Methods:

• Partitioning of two series of small model peptides into neutral phospholipid membranes was measured.
• An interfacial hydrophobicity scale was developed, incorporating the contribution of the peptide bond.
• Free energy scales were used to analyze residue preferences at the membrane interface.

Main Results:

• Aromatic residues are significantly favored at the membrane interface.
• Charged residues and the peptide bond exhibit similar, unfavorable partitioning free energies.
• The peptide bond's partitioning cost is substantial, disfavoring its presence at the interface.

Conclusions:

• The determined interfacial hydrophobicity scale provides a quantitative basis for peptide partitioning.
• The high energetic cost of the peptide bond at the interface is a key factor in structure formation.
• Reducing the peptide bond's partitioning cost via hydrogen bonding may promote secondary structure formation in membrane interfaces.