The intrinsically disordered and amyloidogenic protein α-synuclein (AS) has been linked to several neurodegenerative states, including Parkinson's disease. Here, nanoelectrospray-ionization mass spectrometry (nano-ESI-MS), ion mobility (IM), and native top-down electron transfer dissociation (ETD) techniques are employed to study AS interaction with small molecules known to modulate its aggregation, such as epigallocatechin-3-gallate (EGCG) and dopamine (DA). The complexes formed by the two ligands under identical conditions reveal peculiar differences. While EGCG engages AS in compact conformations, DA preferentially binds to the protein in partially extended conformations. The two ligands also have different effects on AS structure as assessed by IM, with EGCG leading to protein compaction and DA to its extension. Native top-down ETD on the protein-ligand complexes shows how the different observed modes of binding of the two ligands could be related to their known opposite effects on AS aggregation. The results also show that the protein can bind either ligand in the absence of any covalent modifications, such as oxidation.
Konijnenberg, A., Ranica, S., Narkiewicz, J., Legname, G., GRANDORI, R., Sobott, F., et al. (2016). Opposite Structural Effects of Epigallocatechin-3-gallate and Dopamine Binding to α-Synuclein. ANALYTICAL CHEMISTRY, 88(17), 8468-8475 [10.1021/acs.analchem.6b00731].
Citazione: | Konijnenberg, A., Ranica, S., Narkiewicz, J., Legname, G., GRANDORI, R., Sobott, F., et al. (2016). Opposite Structural Effects of Epigallocatechin-3-gallate and Dopamine Binding to α-Synuclein. ANALYTICAL CHEMISTRY, 88(17), 8468-8475 [10.1021/acs.analchem.6b00731]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
Titolo: | Opposite Structural Effects of Epigallocatechin-3-gallate and Dopamine Binding to α-Synuclein | |
Autori: | Konijnenberg, A; Ranica, S; Narkiewicz, J; Legname, G; GRANDORI, R; Sobott, F; NATALELLO, A | |
Autori: | NATALELLO, ANTONINO (Ultimo) (Corresponding) | |
Data di pubblicazione: | 2016 | |
Lingua: | English | |
Rivista: | ANALYTICAL CHEMISTRY | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1021/acs.analchem.6b00731 | |
Appare nelle tipologie: | 01 - Articolo su rivista |
File in questo prodotto:
File | Descrizione | Tipologia | Licenza | |
---|---|---|---|---|
acs.analchem.6b00731_Konijnenberg2016.pdf | Articolo principale | Publisher's version | Administrator Richiedi una copia | |
AnalChem 2016 Author Version.pdf | Articolo principale_Versione Autore | Postprint | Open Access Visualizza/Apri | |
ac6b00731_si_001_SI.pdf | dati supplementari | Publisher's version | Open Access Visualizza/Apri | |
1_Natalello_2016_acs.analchem.6b00731.pdf | Publisher's version | Administrator Richiedi una copia |