title: New model for polymerization of oligomeric alcohol dehydrogenases into nanoaggregates.
abstract: Polymerization and self-assembly of proteins into nanoaggregates of different sizes and morphologies (nanoensembles or nanofilaments) is a phenomenon that involved problems in various neurodegenerative diseases (medicine) and enzyme instability/inactivity (biotechnology). Thermal polymerization of horse liver alcohol dehydrogenase (dimeric) and yeast alcohol dehydrogenase (tetrameric), as biotechnological ADH representative enzymes, was evaluated for the development of a rational strategy to control aggregation. Constructed ADH nuclei, which grew to larger amorphous nanoaggregates, were prevented via high repulsion strain of the net charge values. Good correlation between the variation in scattering and lambda(-2) was related to the amorphousness of the nanoaggregated ADHs, shown by electron microscopic images. Scattering corrections revealed that ADH polymerization was related to the quaternary structural changes, including delocalization of subunits without unfolding, i.e. lacking the 3D conformational and/or secondary-ordered structural changes. The results demonstrated that electrostatic repulsion was not only responsible for disaggregation but also caused a delay in the onset of aggregation temperature, decreasing maximum values of aggregation and amounts of precipitation. Together, our results demonstrate and propose a new model of self-assembly for ADH enzymes based on the construction of nuclei, which grow to formless nanoaggregates with minimal changes in the tertiary and secondary conformations.
authors.affiliation: Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Barzegar
authors.forename: Ali A
authors.initials: AA
authors.lastname: Moosavi-Movahedi
authors.forename: Anahita
authors.initials: A
authors.lastname: Kyani
authors.forename: Bahram
authors.initials: B
authors.lastname: Goliaei
authors.forename: Shahin
authors.initials: S
authors.lastname: Ahmadian
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry*; D000818:Animals; D004795:Enzyme Stability; D006736:Horses; D006863:Hydrogen-Ion Concentration; D008027:Light; D008099:Liver / Q000201:enzymology; D008854:Microscopy, Electron; D049329:Nanostructures / Q000737:chemistry*; D009391:Nephelometry and Turbidimetry; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D012542:Scattering, Radiation; D055672:Static Electricity
chemical_list: D000426:Alcohol Dehydrogenase