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

Salto

Congreso; Latin American Crosstalk in Biophysics and Physiology; 2015

Sociedad Argentina de Biofísica y Seccional Biofísica de la Sociedad Uruguaya de Biociencias

Membrane tension as a physiological mechanism thatmodulates water permeability in human Aquaporin 1SBF.uyToriano R1., Rosi P2., Miranda L2., Costa Almar F1., Paredes M1., Lenze M1., Ozu M1.,Dorr R1.1Lab de Biomembranas, Inst.de Fisiologia y Biofisica "Bernardo Houssay" - CONICET- UBA.2Laboratorio de Síntesis Inorgánica Avanzada. Departamento de Química Inorgánica, Analítica yQuímica Física. FCEyN, UBACorresponding author: rtoriano@fmed.uba.ar roxanatoriano @yahoo.com.arThe Aquaporins (AQPs) are a family of tetrameric membrane integral proteins whichfacilitate water transport across the cell membrane. Each monomer of AQPs contains awater channel. Our former in vitro results showed that human AQP1 (hAQP1) isregulated by increments in membrane-tension1. Our present goal was to studyconformational changes in hAQP1 structure as a putative physiological way to modifywater permeability in cells. In silico experiments were performed by MolecularDynamics Simulations (MDS), using PDB templates of two hAQP1 structures depositedin Protein Data Bank under codes 1FQY and 4CSK: 3.8 Å resolution 1FQY structuresolved by electron crystallography containing 269 residues2 and 3.28 Å resolution4CSK structured solved by X-ray diffraction containing 292 residues3. MDSexperiments (50ns in explicit aqueous solvent) were carried out under two differentconditions: unrestricted and restricted α-Carbon. In this latter one, only α-Carbons in thelipophilic region of the monomers were fixed thus this condition resembles theanchoring of the protein in the cellular membrane. Both the isolated monomer and themonomer inside the tetramers were studied. To analyze the water channel profile alongdynamic experiments we used the PoreWalker server. Furthermore, structuraldescriptors -the distances between specific residues located either in the selectivityregion of the pore or in the NPA site or residues between loop A and the NPA site andbetween loop A and the central pore of the tetramer- were used to evaluateconformational changes.Conclusions: The tetrameric conformation maintains the structure and functionality ofeach monomer which might have an independent behavior regarding water movement.Environmental influences can cause conformational changes that might modulate waterpermeability eventhough AQP1 was described as a constitutively open channel Loops Ainteract with their neighbor monomers and they move in the tetramer independentlyfrom each other.References:[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.