Intra-helical salt-bridge and helix destabilizing residues within the same helical turn: Role of functionally important loop E half-helix in channel regulation of major intrinsic proteins

摘要: Abstract The superfamily of major intrinsic proteins (MIPs) includes aquaporin (AQP) and aquaglyceroporin (AQGP) it is involved in the transport water neutral solutes across membrane. Diverse MIP sequences adopt a unique hour-glass fold with six transmembrane helices (TM1 to TM6) two half-helices (LB LE). Loop E contains one conserved NPA motifs contributes residues aromatic/arginine selectivity filter. Function regulation majority channels are not yet characterized. We have analyzed loop region 1468 their structural models from different organism groups. They can be phylogenetically clustered into AQGPs, AQPs, plant MIPs other MIPs. LE half-helix all AQGPs an intra-helical salt-bridge helix-breaking Gly/Pro within same helical turn. All non-AQGPs lack this but helix destabilizing Gly and/or Pro positions. However, segment connecting TM6 longer by 10–15 compared non-AQGPs. speculate that will relatively more flexible could functionally important. Molecular dynamics simulations on glycerol-specific GlpF, water-transporting AQP1, its mutant fungal AQP channel confirm these predictions. Thus distinct regions E, non-AQGPs, seem capable modulating transport. These also act conjunction extracellular residues/segments regulate