New Model for Polymerization of Oligomeric Alcohol Dehydrogenases into Nanoaggregates |
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Authors: | Abolfazl Barzegar Ali A Moosavi-Movahedi Anahita Kyani Bahram Goliaei Shahin Ahmadian and Nader Sheibani |
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Institution: | (1) Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran;(2) Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran;(3) Foundation for Advancement of Science and Technology in Iran (FAST-IR), Tehran, Iran;(4) Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA;(5) Department of Pharmacology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA; |
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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 λ
−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. |
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