Pathological ATX3 Expression Induces Cell Perturbations in E. coli as Revealed by Biochemical and Biophysical Investigations
Ami, Diletta (University of Milano-Bicocca. Department of Biotechnologies and Biosciences)
Mereghetti, Paolo (Bioinformatics Consultant)
Falvo, Jacopo (University of Milano-Bicocca. Department of Biotechnologies and Biosciences)
Catelani, Tiziano (University of Milano-Bicocca. Department of Biotechnologies and Biosciences)
Visentin, Cristina (Università degli Studi di Milano. Department of Biosciences)
Tortora, Paolo (University of Milano-Bicocca. Department of Biotechnologies and Biosciences)
Ventura, Salvador (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Natalello, Antonino (University of Milano-Bicocca. Departament of Biotechnology and Biosciences)
Regonesi, Maria Elena (Università di Milano-Bicocca. Dipartimento di Biotecnologie e Bioscienze)
Sciandrone, Barbara (University of Milano-Bicocca. Department of Biotechnologies and Biosciences)

Data:	2021
Resum:	Amyloid aggregation of human ataxin-3 (ATX3) is responsible for spinocerebellar ataxia type 3, which belongs to the class of polyglutamine neurodegenerative disorders. It is widely accepted that the formation of toxic oligomeric species is primarily involved in the onset of the disease. For this reason, to understand the mechanisms underlying toxicity, we expressed both a physiological (ATX3-Q24) and a pathological ATX3 variant (ATX3-Q55) in a simplified cellular model, Escherichia coli. It has been observed that ATX3-Q55 expression induces a higher reduction of the cell growth compared to ATX3-Q24, due to the bacteriostatic effect of the toxic oligomeric species. Furthermore, the Fourier transform infrared microspectroscopy investigation, supported by multivariate analysis, made it possible to monitor protein aggregation and the induced cell perturbations in intact cells. In particular, it has been found that the toxic oligomeric species associated with the expression of ATX3-Q55 are responsible for the main spectral changes, ascribable mainly to the cell envelope modifications. A structural alteration of the membrane detected through electron microscopy analysis in the strain expressing the pathological form supports the spectroscopic results.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Ataxin-3 expression ; Amyloids ; Escherichia coli ; FTIR microspectroscopy ; Multivariate analysis ; Oligomer toxicity ; Protein aggregation
Publicat a:	International journal of molecular sciences, Vol. 22, Issue 2 (January 2021) , art. 943, ISSN 1422-0067

DOI: 10.3390/ijms22020943
PMID: 33477953

21 p, 5.3 MB

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