pH-mediated gating and formate transport mechanism in the Escherichia coli formate channel

Abstract

Formate channels play a crucial role in the metabolism of several different kinds of bacteria by bringing about uptake and export of formate ions. The current study investigates the structure, dynamics and ion channel activity of the formate channel FocA from Escherichia coli by employing extensive molecular dynamics (MD) simulations. The channel, known to be pH-sensitive, is modelled under different pH conditions by considering two different protonation states of a histidine residue. The results show that a fall in pH brings about an enhancement of the formate-conducting activity of the channel. The increased conductivity is a consequence of an overall widening of the pore at low pH, with the widening being brought about by movements of a pore-facing helical domain and a loop region. A fall in pH also enhances interactions between formate and the channel, leading to a lowering of the free energy barrier corresponding to formate transport. The findings provide detailed insights into how changes in pH can affect the shuttling of formate into and out of cells in physiologically important bacteria like enteric bacteria.

Keywords:

• Molecular dynamics
• free energy calculations
• formate channel
• gating
• ion transport