Biochemistry Questions Biochemistry Questions / Discuss the significance of the NPA motif in aquaporins.

The NPA motif is a highly conserved sequence of amino acids found in aquaporins, acting as a selectivity filter. This sequence of asparagine-proline-alanine residues is able to form hydrogen bonds with the two lone pairs of electrons found on the oxygen of water molecules. By forming these interactions, the channel protein is able to ‘break’ the chain of water molecules and prevent the transduction of hydronium or H+ ions across the membrane. This is of great interest to the cell, as it prevents the loss of H+ gradients, allowing the production of ATP by the ATP synthase enzyme. By having these residues present on the two half-helices, which also provide a narrow gap through which only small molecules are able to fit, the slight positive dipole also allows the repulsion of positively-charged protons. This sequence of amino acids (NPA) is highly conserved, being found in the selectivity filters of all mammalian aquaporins. This demonstrates the importance of having this motif, and how evolution has not (yet!) found a better way to control transport of water molecules across a membrane. By using an aquaporin, a cell can allow higher rates of water transport than just simple diffusion across the plasma membrane. This is beneficial in the kidneys, where renal water reabsorption is important in the maintenance of blood pressure and concentrations. Aquaporin presence on the cells of the loop of Henle can be increased by hormonal responses, including by vasopressin.