New model for polymerization of oligomeric alcohol dehydrogenases into nanoaggregates.

Publications // Sheibani Lab // Feb 01 2010

PubMed ID: 19444390

Author(s): Barzegar A, Moosavi-Movahedi AA, Kyani A, Goliaei B, Ahmadian S, Sheibani N. New model for polymerization of oligomeric alcohol dehydrogenases into nanoaggregates. Appl Biochem Biotechnol. 2010 Feb;160(4):1188-205. doi: 10.1007/s12010-009-8646-4. Epub 2009 May 15. PMID 19444390

Journal: Applied Biochemistry And Biotechnology, Volume 160, Issue 4, Feb 2010

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.