title: Amyloid-like aggregates formation by bovine apo-carbonic anhydrase in various alcohols: A comparative study.
abstract: Peptides and proteins convert from their native states to amyloid fibrillar aggregates in a number of pathological conditions. Characterizing these species could provide useful information on their pathogenicity and the key factors involved in their generation. In this study, we have observed the ability of the model protein apo-bovine carbonic anhydrase (apo-BCA) to form amyloid-like aggregates in the presence of halogenated and non-halogenated alcohols. Far-UV circular dichroism, ThT fluorescence, atomic force microscopy and dynamic light scattering were used to characterize these structures. The concentration required for effective protein aggregation varied between the solvents, with non-halogenated alcohols acting in a wider range. These aggregates show amyloid-like structures as determined by specific techniques used for characterizing amyloid structures. Oligomers were obtained with various size distributions, but fibrillar structures were not observed. Use of halogenated alcohols resulted into smaller hydrodynamic radii, and most stable oligomers were formed in hexafluoropropan-2-ol (HFIP). At optimal concentrations used to generate these structures, the non-halogenated alcohols showed higher hydrophobicity, which may be related to the lower stability of the generated oligomers. These oligomers have the potential to be used as models in the search for effective treatments in proteinopathies.
authors.affiliation: Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran. Electronic address: ashaghi@gmail.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Es-Haghi
authors.affiliation: Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Ebrahim-Habibi
authors.affiliation: Department of Andrology at Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Sabbaghian
authors.affiliation: Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nemat-Gorgani
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D052160:Benzothiazoles; D002256:Carbonic Anhydrases / Q000737:chemistry*; D002417:Cattle; D000067493:Dynamic Light Scattering; D057446:Hydrodynamics; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D018625:Microscopy, Atomic Force; D066329:Protein Aggregates; D012996:Solutions; D013844:Thiazoles / Q000737:chemistry; D013997:Time Factors; D014270:Trifluoroethanol / Q000737:chemistry
chemical_list: D000438:Alcohols; D000682:Amyloid; D052160:Benzothiazoles; D066329:Protein Aggregates; D012996:Solutions; D013844:Thiazoles; C009462:thioflavin T; D014270:Trifluoroethanol; D002256:Carbonic Anhydrases
keywords: Alcohol; Carbonic anhydrase; HFIP; Metalloprotein; Pre-molten globule