Inward-facing glycine residues create sharp turns in β-barrel membrane proteins

The transmembrane region of outer-membrane proteins (OMPs) of Gram-negative bacteria are almost exclusively beta-barrels composed of between 8 and 26 beta-strands. To explore the relationship between beta-barrel size and shape, we modeled and simulated engineered variants of the Escherichia coli protein OmpX with 8, 10, 12, 14, and 16 beta-strands. We found that while smaller barrels maintained a roughly circular shape, the 16-stranded variant developed a flattened cross section. This flat cross section impeded its ability to conduct ions, in agreement with previous experimental observations. Flattening was determined to arise from the presence of inward-facing glycines at sharp turns in the beta-barrel. An analysis of all simulations revealed that glycines, on average, make significantly smaller angles with residues on neighboring strands than all other amino acids, including alanine, and create sharp turns in beta-barrel cross sections. This observation was generalized to 119 unique structurally resolved OMPs. We also found that the fraction of glycines in beta-barrels decreases as the strand number increases, suggesting an evolutionary role for the addition or removal of glycine in OMP sequences.

Automated summary

The research focused on the transmembrane region of outer-membrane proteins in Gram-negative bacteria, specifically looking at the relationship between beta-barrel size and shape. The study found that smaller beta-barrels maintained a circular shape, while larger variants developed a flattened cross section due to the presence of inward-facing glycines. It was also observed that as the number of beta-strands increased, the fraction of glycines in beta-barrels decreased, possibly indicating an evolutionary role in OMP sequences.