Aquaporins (AQPs) are homotetrameric channel proteins allowing the diffusion of water/small solutes across membranes. AQP structures are very similar, with each monomer defining a single pore selective to water/solutes and contributing to form a fifth central pore, whose meaning remains elusive. Nevertheless, AQPs show distinct transport selectivity to water, orthodox AQPs, or glycerol/solutes, aquaglyceroporins. The variety of available AQP 3D-structures is a valuable resource for studying the structure-function relationships within this protein family. A recent comparative analysis allowed specific electrostatic profiles to be associated with the main AQP selectivity to water and glycerol. We exploited this approach to gain some insights into the role of the AQP central pore. Interestingly: the electrostatics of AQP central channels correlates with their main transport function; AQP1 and AQP4 fifth pore has strikingly comparable electrostatics, supporting previous works reporting its involvement in the transport of CO2 across membranes; the central pore of the spinach PIP2;1 shares the same electrostatic profile of the monomeric pore of orthodox AQPs, suggesting that the fifth pore could allegedly represent an alternative/additional path for the transport of water across (at least some) plant AQPs. The hypothesis is being verified experimentally.

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