Dynamics of Phosphate Transport by the Anion-specific Outer Membrane Protein OprP

Abstract

The outer membrane protein P (OprP) from Pseudomonas aeruginosa forms a water-filled channel which has an enhanced selectivity for anions, especially phosphates. The structure of this homotrimeric protein (PDB code 2O4V) reveals three positively charged loops (L3, L5, and T7) which are folded into the lumen and are suggested to funnel anions into the pore. Steered molecular dynamics (SMD) simulations have been performed to better understand the mechanism of the phosphate transport. In these SMD simulations an external force was applied to pull a phosphate anion from the extracellular to periplasmic side and vice versa. The SMD results have been supplemented by unbiased molecular dynamics (MD) simulations. The SMD force profiles and the phosphate trajectories reveal energy wells close to the L5, L3, and T7 regions. The dominant wells are identified at the L3 (or constriction) region, while the others are at the extracellular L5 and periplasmic T7 regions. Both the SMD and MD simulations suggest that favourable interactions with the side chains of positively charged amino acids contribute to the phosphate-protein binding site. The results of our studies suggest a full possible pathway for phosphate transport.