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

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.