title: Role of electrostatics on membrane binding, aggregation and destabilization induced by NAD(P)H dehydrogenases. Implication in membrane fusion.
abstract: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a classical glycolytic protein that can promote the fusion of phospholipid vesicles and can also play a vital role on in vivo fusogenic events. However, it is not clear how this redox enzyme, which lack conserved structural or sequence motifs related to membrane fusion, catalyze this process. In order to detect if this ability is present in other NAD(P)H dehydrogenases with available structure, spectroscopic studies were performed to evaluate the capability of alcohol dehydrogenase (ADH), glutamic dehydrogenase (GDH) and sorbitol dehydrogenase (SDH) to bind, aggregate, destabilize and fuse vesicles. Based on finite difference Poisson-Boltzmann calculations (FDPB) the protein-membrane interactions were analyzed. A model for the protein-membrane complex in its minimum free energy of interaction was obtained for each protein and the amino acids involved in the binding processes were suggested. A previously undescribed relationship between membrane destabilization and crevices with high electropositive potential on the protein surface was proposed. The putative implication of the non-specific electrostatics on NAD(P)H dehydrogenases induced membrane fusion is discussed.
authors.affiliation: Departamento Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (CONICET-UNT) and Instituto de Química Biológica Dr. Bernabé Bloj, Chacabuco 461 (4000), Tucumán, Argentina.
authors.forename: César L
authors.initials: CL
authors.lastname: Avila
authors.forename: Beatriz F
authors.initials: BF
authors.lastname: de Arcuri
authors.forename: Fernando
authors.initials: F
authors.lastname: Gonzalez-Nilo
authors.forename: Javier
authors.initials: J
authors.lastname: De Las Rivas
authors.forename: Rosana
authors.initials: R
authors.lastname: Chehín
authors.forename: Roberto
authors.initials: R
authors.lastname: Morero
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D017124:Conserved Sequence; D018086:Glutamate Dehydrogenase (NADP+) / Q000737:chemistry; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000737:chemistry; D007064:L-Iditol 2-Dehydrogenase / Q000737:chemistry; D008561:Membrane Fusion; D008958:Models, Molecular; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D017433:Protein Structure, Secondary; D011817:Rabbits; D012756:Sheep; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D013816:Thermodynamics; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D053835:Unilamellar Liposomes; C042511:1,2-dioleoylphosphatidylserine; D000426:Alcohol Dehydrogenase; D007064:L-Iditol 2-Dehydrogenase; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); D018086:Glutamate Dehydrogenase (NADP+); D009247:NADH, NADPH Oxidoreductases; C017251:1,2-oleoylphosphatidylcholine