Mechanistics insights of hydrogen peroxide transport through PIP aquaporins pore

Abstract

Hydrogen peroxide (H2O2) is transported through membranes by aquaporins (AQP). In particular, some plant PIP aquaporins isoforms are efficient H2O2 channels. As water and H2O2 share physicochemical features, it was first supposed that all AQP that transport water could act as an H2O2 channel. However, experimental evidence showed that not all PIP that transport water can transport H2O2. So, the mechanism of H2O2 transport is still an unsolved issue for AQP channels. MtPIP2,3 is a plasma membrane AQP from the legume Medicago truncatula that permeates H2O2. To understand the structural and chemical selectivity mechanisms leading to H2O2 permeability in PIPs, we characterized the particularities of H2O2 passingthrough MtPIP2,3 pore by 1 μs atomistic molecular dynamic simulations. As PIPs are tetrameric pH gated channels we constructed homology MtPIP2,3 models in open and closed states, and with or without H2O2. All models were conformationally stable along the simulation and H2O2 permeation events were found in the simulations in the presence of this molecule. We find that: i- H2O2 molecules can cross the pore in a single file, iidihedral angles adopted by H2O2 along the pore Z axis present a different distribution compared to the angles visited in the solution; in the selectivity-determining NPA region, H2O2 adopts the wider range of dihedral angles, iii- higher residence times are located around the selectivity filter zone in the open channel and moves to the cytoplasmic filterarea in the closed channel; and iv- the constriction in the cytoplasmic filter area seems to be more stringent for H2O2 passage than for water.Our results shed light onto the molecular mechanism of H2O2 passage through MtPIP2,3 and represent the first steps to understand the structural determinants of AQP differential selectivity for these molecules and water.