Research on Parkinson's disease most often focuses on the ability of the protein α-synuclein (α-syn) to form oligomers and amyloid fibrils, and how such species promote brain death. However, there are indications that α-syn also plays a gene-regulatory role in the cell nucleus. Noncanonical tetrahelical nucleic acids, G-quadruplexes (G4Q), and i-motifs have been shown to play an important role in the control of genomic events. Using the conformation-sensitive single-molecule Förster resonance energy transfer technique we show that monomeric and oligomeric α-syn affect G4Qs and i-motifs in a different way and lead to remodeling of their conformational substates. Aggregated α-syn destabilizes the G4Q leading to unfolding. In contrast, both monomeric and aggregated α-syn enhance folding of the i-motif sequence of telomeric DNA. Importantly, macromolecular crowding is able to partially rescue G4Q from unfolding.

Remodeling of the Conformational Dynamics of Noncanonical DNA Structures by Monomeric and Aggregated α-Synuclein / Knop, Jim-Marcel; Mukherjee, Sanjib K; Oliva, Rosario; Möbitz, Simone; Winter, Roland. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 1520-5126. - 142:43(2020), pp. 18299-18303. [10.1021/jacs.0c07192]

Remodeling of the Conformational Dynamics of Noncanonical DNA Structures by Monomeric and Aggregated α-Synuclein

Oliva, Rosario;
2020

Abstract

Research on Parkinson's disease most often focuses on the ability of the protein α-synuclein (α-syn) to form oligomers and amyloid fibrils, and how such species promote brain death. However, there are indications that α-syn also plays a gene-regulatory role in the cell nucleus. Noncanonical tetrahelical nucleic acids, G-quadruplexes (G4Q), and i-motifs have been shown to play an important role in the control of genomic events. Using the conformation-sensitive single-molecule Förster resonance energy transfer technique we show that monomeric and oligomeric α-syn affect G4Qs and i-motifs in a different way and lead to remodeling of their conformational substates. Aggregated α-syn destabilizes the G4Q leading to unfolding. In contrast, both monomeric and aggregated α-syn enhance folding of the i-motif sequence of telomeric DNA. Importantly, macromolecular crowding is able to partially rescue G4Q from unfolding.
2020
Remodeling of the Conformational Dynamics of Noncanonical DNA Structures by Monomeric and Aggregated α-Synuclein / Knop, Jim-Marcel; Mukherjee, Sanjib K; Oliva, Rosario; Möbitz, Simone; Winter, Roland. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 1520-5126. - 142:43(2020), pp. 18299-18303. [10.1021/jacs.0c07192]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/892862
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