Membrane tension as a physiological mechanism that modulates water permeability in human Aquaporin 1

TORIANO, ROXANA; ROSI, PABLO; MIRANDA, LUCAS; COSTA ALMAR, FLORENCIA; PAREDES, MARYANT; LENZE, MARIELA; OZU, MARCELO; DORR, RICARDO A.

Salto

Congreso; Latin American Crosstalk in Biophysics and Physiology; 2015

The Aquaporins (AQPs) are a family of tetrameric membrane integralproteins which facilitate water transport across the cell membrane. Eachmonomer of AQPs contains a water channel. Our former in vitro resultsshowed that human AQP1 (hAQP1) is regulated by increments in membrane-tension1. Our present goal was to study conformational changes in hAQP1structure as a putative physiological way to modify water permeability incells. In silico experiments were performed by Molecular DynamicsSimulations (MDS), using PDB templates of two hAQP1 structures depositedin Protein Data Bank under codes 1FQY and 4CSK: 3.8 Å resolution 1FQYstructure solved by electron crystallography containing 269 residues2 and3.28 Å resolution 4CSK structured solved by X-ray diffraction containing292 residues3. MDS experiments (50ns in explicit aqueous solvent) werecarried out under two different conditions: unrestricted and restricted α-Carbon. In this latter one, only α-Carbons in the lipophilic region of themonomers were fixed thus this condition resembles the anchoring of theprotein in the cellular membrane. Both the isolated monomer and themonomer inside the tetramers were studied. To analyze the water channelprofile along dynamic experiments we used the PoreWalker server.Furthermore, structural descriptors -the distances between specific residueslocated either in the selectivity region of the pore or in the NPA site orresidues between loop A and the NPA site and between loop A and the centralpore of the tetramer- were used to evaluate conformational changes. Conclusions: The tetrameric conformation maintains the structure andfunctionality of each monomer which might have an independent behaviorregarding water movement. Environmental influences can causeconformational changes that might modulate water permeability eventhoughAQP1 was described as a constitutively open channel Loops A interact withtheir neighbor monomers and they move in the tetramer independently fromeach other.[1] Ozu M, Dorr RA, Gutiérrez F, Politi MT and Toriano R. Biophysical Journal 104:85?95.2013[2] Murata K., Nature 407: 599-605, 2000.[3] Ruiz Carrillo D. et al. Acta Crystallogr.,Sect.F 70: 1657, 2014