Molecular characterization and structural dynamics of Aquaporin1 from walking catfish in lipid bilayers

Abstract

Aquaporin's (AQPs) are the major superfamily of small integral membrane proteins that facilitates transportation of water, urea, ammonia, glycerol and ions across biological cell membranes. Despite of recent advancements made in understanding the biology of Aquaporin's, only few isoforms of aquaporin 1 (AQP1) some of the teleost fish species have been characterized at molecular scale. In this study, we made an attempt to elucidate the molecular mechanism of water transportation in AQP1 from walking catfish (Clarias batrachus), a model species capable of breathing in air and inhabits in challenging environments. Using state-of-the-art computational modelling and all-atoms molecular dynamics simulation, we explored the structural dynamics of full-length aquaporin 1 from walking catfish (CbAQP1) in lipid mimetic bilayers. Unlike AQP1 of human and bovine, structural ensembles of CbAQP1 from MD revealed discrete positioning of pore lining residues at the intracellular end. Snapshots from MD simulation displayed differential dynamics of aromatic/arginine (ar/R) filter and extracellular loop C bridging transmembrane (TM) helix H3 and H4. Distinct conformation of large extracellular loops, loop bridging TM2 domain and HB helix along with positioning of selectivity filter lining residues controls the permeability of water across the bilayer. Moreover, the identified unique and conserved lipid binding sites with 100% lipid occupancy signifies lipid mediated structural dynamics of CbAQP1. All-together, this is the first ever report on structural-dynamics of aquaporin 1 in walking catfish which will be useful to understand the molecular basis of transportation of water and other small molecules under varying degree of hyperosmotic environment.