The Relationship between Structural Symmetry and Function in Membrane Proteins

Abstract

Membrane proteins are encoded by 20-30% of genomes and play key roles in a number of diverse functions. Many structures of membrane proteins have been reported to exhibit symmetry and pseudo-symmetry both between subunits and within a subunit. These symmetries are not only striking, but also important because structurally symmetric regions often appear to relate to the functional properties of a protein. However, this symmetry-function relationship has not been studied systematically in membrane proteins. To establish the role of symmetry in membrane protein function, we analyzed the structures contained in the Encyclopedia of Membrane Proteins Analyzed by Structure and Symmetry (EncoMPASS) database. A taxonomic analysis on this dataset revealed similar ratios of symmetry in bacteria, eukarya, and archaea. To identify the functions associated with specific symmetry features, a functional symmetry enrichment analysis was performed using the Gene Ontology (GO) and Transporter Classification Database (TCDB) annotations for each structure. To investigate the relationship between structural symmetry and cellular location a membrane localization enrichment analysis was performed using data from the Orientations of Proteins in Membranes (OPM) database. We found that the functional annotations can be explained using physiological and mechanistic reasoning. For example, the C4 symmetry group was significantly enriched in potassium ion transport and cation channel activity, where the C4 symmetry around a central pore allows for the coordination of ions through the membrane. The membrane localization analysis showed that structural symmetry appears to be unrelated to the location of the membrane within the cell. This study provides the first systematic investigation of the symmetry-function relationship in membrane proteins.