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

Abstract

A total of 1311 homodimers were collected and analyzed in three different categories to highlight the impact of lipid environment and secondary structure type: 422 cytoplasmic α-helix, 411 cytoplasmic β-strand, and 478 membrane complexes. Structural features of the interface connecting two monomers were investigated and compared to those of the non-interface surface. Every residue on the surface of each monomer was explored based on four attributes: solvent-accessible surface area (SASA), protrusion index (Cx), surface planarity, and surface roughness. SASA and Cx distribution profiles clearly distinguished the interface from the surface in all categories, where the rim of the interface displayed higher SASA and Cx values than the rest of the surface. Surface residues in membrane complexes protruded less than cytoplasmic ones due to the hydrophobic environment, and consequently, the difference between surface and interface residues became less noticeable in that category. Cytoplasmic β-strand complexes displayed markedly lower SASA at the interface core than at the surface. The major distinction between the surface and interface was achieved through surface roughness, which displayed significantly higher values for the interface than the surface, especially in cytoplasmic complexes. Clearly, a surface which is relatively rugged favors the association of two monomers through multiple van der Waals interactions and hydrogen-bond formations. Another structural descriptor with strong distinguishing ability was surface planarity, which was higher at the interface than at the non-interface surface. Surface flatness would eventually facilitate the interconnectedness of an interface with a network of residue pairs bridging two complementary surfaces. Analysis of contact pairs revealed that hydrophobic pairs have the highest frequency of occurrence in the lipid environment of membrane complexes. However, despite the scarcity of polar residues at the interface, the likelihood of observing a contact between polar residues was markedly higher than that of hydrophobic ones. © 2025 The Authors. Published by American Chemical Society.