Aquaporins: More than functional monomers in a tetrameric arrangement

Abstract

Aquaporins (AQPs) function as tetrameric structures in which each monomer has its ownpermeable pathway. The combination of structural biology, molecular dynamics simulations, andexperimental approaches has contributed to improve our knowledge of how protein conformationalchanges can challenge its transport capacity, rapidly altering the membrane permeability. This reviewis focused on evidence that highlights the functional relationship between the monomers and thetetramer. In this sense, we address AQP permeation capacity as well as regulatory mechanismsthat affect the monomer, the tetramer, or tetramers combined in complex structures. We thereforeexplore: (i) water permeation and recent evidence on ion permeation, including the permeation pathwaycontroversy?each monomer versus the central pore of the tetramer?and (ii) regulatory mechanismsthat cannot be attributed to independent monomers. In particular, we discuss channel gating andAQPs that sense membrane tension. For the latter we propose a possible mechanism that includes themonomer (slight changes of pore shape, the number of possible H-bonds between water molecules andpore-lining residues) and the tetramer (interactions among monomers and a positive cooperative effect).