Charge Asymmetry in Outer Membrane Proteins

Abstract

Outer membrane proteins are the proteins found in the outer membranes of bacteria, mitochondria and chloroplasts. These proteins adopt a beta barrel structure. There are thousands of outer membrane beta barrels reported in genomic databases with approximately 2-3% of the genes in gram-negative bacteria encoding these proteins. Of the non-redundant outer membrane protein structures in the Protein Data Bank, half have been solved over the past 5 years. This influx of information provides new opportunities for understanding the chemistry of these proteins.Using a structural bioinformatics approach, we have determined a strong asymmetry in the charge distribution of these proteins. For the outward-facing amino acids of the beta barrel within regions of similar amino acid density for both membrane leaflets, the external side of the membrane contains more than three times the number of charged amino acids as the internal side of the membrane. Moreover, the lipid bilayer of the outer membrane is asymmetric, and the overall preference for amino acid types to be in the external leaflet of the membrane correlates roughly with the hydrophobicity of the membrane lipids. This preference is demonstrably related to the difference in lipid composition of the external and internal leaflets of the membrane. The charge asymmetry of proteins in the outer membrane has important implications for how we understand the mechanism of outer membrane protein insertion.