Does CO2 permeate through aquaporin-1?

Abstract

Aquaporins facilitate water permeation across biological membranes. Additionally, glycerol and other small neutral solutes are permeated by related aquaglyceroporins. The role of aquaporins in gas permeation has been a long-standing and controversially discussed issue. We present an extensive set of atomistic molecular dynamics simulations that address the question of CO(2) permeation through human aquaporin-1. Free energy profiles derived from the simulations display a barrier of approximately 23 kJ/mol in the aromatic/arginine constriction region of the water pore, whereas a barrier of approximately 4 kJ/mol was observed for a palmitoyloleoylphosphatidylethanolamine lipid bilayer membrane. The results indicate that significant aquaporin-1-mediated CO(2) permeation is to be expected only in membranes with a low intrinsic CO(2) permeability.

FIGURE 1

(a) Typical simulation setup of an AQP1 tetramer, solvated in a POPE bilayer and water. Five CO₂ molecules in bulk water are shown in blue and red. (b) In the top view, the four monomeric water pores and the central cavity can be identified. (c) A snapshot taken from an equilibrium simulation showing a water pore (helices and ribbon representation) filled by a single file of water, and the central cavity along the fourfold axis of the tetramer (surface representation). The surface representation is colored according to residue hydrophobicity: hydrophobic residues in orange, hydrophilic residues in blue. All figures with molecular representations were made with PyMOL (50).

FIGURE 2

Free energy profile for CO₂ permeation through the aquaporin-1 water pore (black, solid line), the tetrameric central cavity (black, dashed line), and a POPE bilayer (shaded).

FIGURE 3

Trajectories of unrestrained CO₂ molecules in the monomeric AQP1 channel (a), and profiles of enthalpic interactions of CO₂ with water (green), protein or POPE, respectively (blue), and total (red) together with the free energy profiles of (cf. Fig. 2, black) for the monomeric channel (b), the central channel around the tetramer axis (c), and through the POPE bilayer (d). The enthalpic profiles only show interactions involving CO₂ and do not contain interactions within the CO₂'s surroundings.

FIGURE 4

Free energy profiles of water through the monomeric AQP1 pore obtained by umbrella simulations (solid) and from evaluation of the water density distribution (shaded).

FIGURE 5

A CO₂ at various positions along the water channel indicating a possible pathway for CO₂ along the NPA motifs and through the aromatic/arginine constriction region. The CO₂ molecule is colored in red and marine blue. On top of the sequence, the corresponding free energy is plotted, indicating the 23 kJ/mol barrier putatively caused by competition for hydrogen bonds with Arg-195. Note that frequent hydrogen bonds between water molecules and Arg-195 break upon CO₂ passage.