Charge asymmetry in the proteins of the outer membrane

Outer membrane beta-barrels (OMBBs) are the proteins found in the outer membrane of bacteria, mitochondria and chloroplasts. There are thousands of beta-barrels reported in genomic databases with ∼2-3% of the genes in gram-negative bacteria encoding these proteins. These proteins have a wide variety of biological functions including active and passive transport, cell adhesion, catalysis and structural anchoring. Of the non-redundant OMBB structures in the Protein Data Bank, half have been solved during the past 5 years. This influx of information provides new opportunities for understanding the chemistry of these proteins. The distribution of charges in proteins in the outer membrane has implications for how the mechanism of outer membrane protein insertion is understood. Understanding the distribution of charges might also assist in organism selection for the heterologous expression of mitochondrial OMBBs. We find a strong asymmetry in the charge distribution of these proteins. For the outward-facing residues of the beta-barrel within regions of similar amino acid density for both membrane leaflets, the external side of the outer membrane contains almost three times the number of charged residues as the internal side of the outer 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.