The behavior of water pore in human aquaporin-1 is influenced by different factors at the cell membrane level

ROSI PABLO; DORR RICARDO; LENZE MARIELA; TORIANO ROXANA

Mar del Plata

Congreso; REUNION CONJUNTA SAIC SAI SAFIS 2018; 2018

SAI SAFIS SAIC

Studies of the structural changes in proteins and how the environment influences on proteins during cell life are becoming more relevant to understand their dynamics and their regulation. The aquaporins are no exception. Working with human Aquaporin-1 (hAQP1) our group has studied the behavior of the protein at different levels by computational methods (mathematical modeling, molecular dynamic simulations (MDS), and protein-protein docking) and experimental methods (video-microscopy, internal pressure measurements and voltage- clamp). On in-vitro experiments using protein expression in X.laevis oocytes, we found that different challenges can modified water transport across hAQP1. We have reported that a decrease on water permeability (Pf) occurs when increasing the membrane tension due to cell swelling and that this behavior is reversible and occurs in a cooperative manner among monomers. Now we studied the dynamic behavior of the hAQP1 water pore by MDS experiments. We examine different molecular descriptors (RMSD, SASA, etc.) in the spatial, temporal and in the frequency domain. 214 variables describing water pore of each of 9 monomers of 3 systems (M, FT and RT) under different conditions of ?lateral restriction? were used to perform PCA and PARAFAC, both multivariate statistical procedures. The results show that restrictions in α-Carbons that face to the lipid bilayer, affect subtly but significantly the behavior of non-restricted sites inside the water pore. On the other hand, our in-vitro experiments show that co-expression of AQP1 plus ENaC makes the cell membrane more elastic than AQP1 expression alone (p