THE PORE REGION OF HUMAN AQUAPORIN-1 IS INFLUENCED BY DISTANT RESTRICTIONS IN α-HELICES. A MOLECULAR DYNAMIC SIMULATION (MDS) APPROACH OVER THE CRYSTALLOGRAPHIC STRUCTURES 1FQY AND 4CSK

CAMARA AMANDA; DORR RICARDO; TORIANO, ROXANA; ROSI PABLO

Congreso; JOINT MEETING OF BIOSCIENCE SOCIETIES; 2017

SAIC, SAIB, SAI, SAA, SAB, SAB, SAFE, SAFIS, SAH, SAP

THE PORE REGION OF HUMAN AQUAPORIN-1 IS INFLUENCED BY DISTANT RESTRICTIONS IN α-HELICES. A MOLECULAR DYNAMIC SIMULATION (MDS) APPROACH OVER THE CRYSTALLOGRAPHIC STRUCTURES 1FQY AND 4CSKHuman Aquaporin-1 (hAQP1) is an integral membrane protein that transports water as canonical function. We have reported that hAQP1 permeability is modulated by changes in membrane tension. To investigate whether this modulation is related to the dynamic conformation of the pore, 1FQY and 4CSK were studied by MDS. For both structures three systems were defined and analyzed: a) tetramer restricted in α-carbons (Cα) in contact with the lipid bilayer (RT); b) tetramer without any further restrictions that those provided by the tetramerization itself (FT); and c) monomer (M). Several descriptors were used for analysis, such as the classical RMSD and Solvent Accessible Surface Area in residues of the NPA and ar/R sites, and original ones as geometric description of 9 sections in the pore and the number of water molecules inside it. When statistical procedures like PCA and PARAFAC were performed, systems were discriminated. Results: 1) the contribution of restricting Cα in tetramers differs from the contribution of tetramerization itself; 2) monomers behave differently within FT and RT; 3) at level of the pore, no descriptor per se explains the differences observed between FT and RT systems; 4) localized restrictions in RT cause modifications in far and not restricted sites inside the pore. Conclusions: The distinct behavior shown by FT, RT and M systems open the possibility to deep in a possible influence of the membrane properties that could modify the permeability of the pore. Our work shows quantitative evidence that restrictions affect, subtle but significantly, the dynamics of the protein at level of the aqueous pore. We also report the need to exhaustively explore the assumptions in the use of MDS, since we have detected differences in the behavior of two structures that describe the same protein. Our findings also confirm the need for further investigations in the relationship of the aquaporins with their lipid environment to understand their fine regulation.