Home > Publications database > Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly > print |
001 | 878039 | ||
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100 | 1 | _ | |a Palomino, Oscar |0 P:(DE-Juel1)174273 |b 0 |u fzj |
245 | _ | _ | |a Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly |
260 | _ | _ | |a Basel |c 2020 |b Molecular Diversity Preservation International |
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520 | _ | _ | |a Recent studies suggest that Tyr-39 might play a critical role for both the normal function and the pathological dysfunction of α-synuclein (αS), an intrinsically disordered protein involved in Parkinson’s disease. We perform here a comparative analysis between the structural features of human αS and its Y39A, Y39F, and Y39L variants. By the combined application of site-directed mutagenesis, biophysical techniques, and enhanced sampling molecular simulations, we show that removing aromatic functionality at position 39 of monomeric αS leads to protein variants populating more compact conformations, conserving its disordered nature and secondary structure propensities. Contrasting with the subtle changes induced by mutations on the protein structure, removing aromaticity at position 39 impacts strongly on the interaction of αS with the potent amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our findings further support the role of Tyr-39 in forming essential inter and intramolecular contacts that might have important repercussions for the function and the dysfunction of αS. |
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536 | _ | _ | |a Exploring the conformational properties of alpha-synuclein variants: an enhanced sampling study (jara0209_20200501) |0 G:(DE-Juel1)jara0209_20200501 |c jara0209_20200501 |f Exploring the conformational properties of alpha-synuclein variants: an enhanced sampling study |x 1 |
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700 | 1 | _ | |a Sacco, Pamela S. |0 P:(DE-HGF)0 |b 2 |
700 | 1 | _ | |a Rossetti, Giulia |0 P:(DE-Juel1)145921 |b 3 |
700 | 1 | _ | |a Carloni, Paolo |0 P:(DE-Juel1)145614 |b 4 |e Corresponding author |
700 | 1 | _ | |a Fernandez, Claudio O. |0 P:(DE-HGF)0 |b 5 |e Corresponding author |
773 | _ | _ | |a 10.3390/ijms21145061 |g Vol. 21, no. 14, p. 5061 - |0 PERI:(DE-600)2019364-6 |n 14 |p 5061 - |t International journal of molecular sciences |v 21 |y 2020 |x 1422-0067 |
856 | 4 | _ | |u https://juser.fz-juelich.de/record/878039/files/Invoice_MDPI_ijms-837050_1589.23EUR.pdf |
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856 | 4 | _ | |u https://juser.fz-juelich.de/record/878039/files/ijms-21-05061-v2.pdf |y OpenAccess |
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