Description of heterogeneous molecular ensembles, such as intrinsically disordered proteins, represents a challenge in structural biology and an urgent question posed by biochemistry to interpret many physiologically important, regulatory mechanisms. Single-molecule techniques can provide a unique contribution to this field. This work applies single molecule force spectroscopy to probe conformational properties of α-synuclein in solution and its conformational changes induced by ligand binding. The goal is to compare data from such an approach with those obtained by native mass spectrometry. These two orthogonal, biophysical methods are found to deliver a complex picture, in which monomeric α-synuclein in solution spontaneously populates compact and partially compacted states, which are differently stabilized by binding to aggregation inhibitors, such as dopamine and epigallocatechin-3-gallate. Analyses by circular dichroism and Fourier-transform infrared spectroscopy show that these transitions do not involve formation of secondary structure. This comparative analysis provides support to structural interpretation of charge-state distributions obtained by native mass spectrometry and helps, in turn, defining the conformational components detected by single molecule force spectroscopy.

Corti, R., Marrano, C., Salerno, D., Brocca, S., Natalello, A., Santambrogio, C., et al. (2019). Depicting conformational ensembles of α-synuclein by single molecule force spectroscopy and native mass spectroscopy. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20(20) [10.3390/ijms20205181].

Depicting conformational ensembles of α-synuclein by single molecule force spectroscopy and native mass spectroscopy

Corti, Roberta
Primo
;
Marrano, Claudia A;Salerno, Domenico;Brocca, Stefania;Natalello, Antonino;Santambrogio, Carlo;Mantegazza, Francesco;Grandori, Rita;Cassina, Valeria
Ultimo
2019

Abstract

Description of heterogeneous molecular ensembles, such as intrinsically disordered proteins, represents a challenge in structural biology and an urgent question posed by biochemistry to interpret many physiologically important, regulatory mechanisms. Single-molecule techniques can provide a unique contribution to this field. This work applies single molecule force spectroscopy to probe conformational properties of α-synuclein in solution and its conformational changes induced by ligand binding. The goal is to compare data from such an approach with those obtained by native mass spectrometry. These two orthogonal, biophysical methods are found to deliver a complex picture, in which monomeric α-synuclein in solution spontaneously populates compact and partially compacted states, which are differently stabilized by binding to aggregation inhibitors, such as dopamine and epigallocatechin-3-gallate. Analyses by circular dichroism and Fourier-transform infrared spectroscopy show that these transitions do not involve formation of secondary structure. This comparative analysis provides support to structural interpretation of charge-state distributions obtained by native mass spectrometry and helps, in turn, defining the conformational components detected by single molecule force spectroscopy.
Articolo in rivista - Articolo scientifico
Intrinsically disordered proteins; Native mass spectrometry; Single molecule force spectroscopy; α-synuclein;
intrinsically disordered proteins; native mass spectrometry; single molecule force spectroscopy; α-synuclein
English
19-ott-2019
2019
20
20
5181
open
Corti, R., Marrano, C., Salerno, D., Brocca, S., Natalello, A., Santambrogio, C., et al. (2019). Depicting conformational ensembles of α-synuclein by single molecule force spectroscopy and native mass spectroscopy. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20(20) [10.3390/ijms20205181].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/246549
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