Figure 6.

Conserved and key residues in the single-file water pathway of AQPs could be involved in the development of gating currents. Molecular representations of AQP1, AQP4 and AtPIP2;1 were developed on the bases of the PDB files 1J4N [58], 3GD8 [63] and 5I32 [84], respectively. The AQP6 model was built by homology modelling utilising the Swiss-Model (https://swissmodel.expasy.org/, 15 September 2022) public server [199,200] and the PDB file 1H6I [52] as templates. In all lateral views, the second transmembrane segment was hidden for better visualization of the water pathway. In all cases, both Asn residues of the NPA region are shown in blue, the His of the selectivity filter (SF) is shown in red and the Arg of the SF is shown in green. In addition, other important residues are indicated in each AQP. In AQP1, the extracellular Cys sensitive to HgCl₂ inhibition is shown in light grey (just next to the SF), and His and Gly from the H-bond donor region at the cytoplasmic opening are shown in red and magenta, respectively. In AQP4, the His sensitive to intracellular pH acidification [26] is shown in red. In AQP6, the Cys involved in ion conductance [25] is shown in dark grey (just next to the SF). In AtPIP2;1, the Gly involved in ion conductance [27] is shown in magenta (in the H-bond donor region of the cytoplasmic mouth). The single file region is defined between the SF and the H-bond donor region located at the cytoplasmic opening (see Figure 3). According to molecular dynamic simulations with human AQP4, the His and the Arg of the SF are candidates to be involved in the development of gating currents in AQPs [170]. All these model representations were built only with the purpose of visualization and do not have further claims. This image was made with VMD v1.9.4a48 software support. VMD is developed with NIH support by the Theoretical and Computational Biophysics group at the Beckman Institute, University of Illinois at Urbana-Champaign.