2020
DOI: 10.3390/ijms21145061
|View full text |Cite
|
Sign up to set email alerts
|

Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly

Abstract: 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 posi… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1

Citation Types

0
7
0

Year Published

2021
2021
2024
2024

Publication Types

Select...
4
1

Relationship

2
3

Authors

Journals

citations
Cited by 5 publications
(7 citation statements)
references
References 72 publications
0
7
0
Order By: Relevance
“…As a result, certain disease-associated PTMs can potentially serve as biomarkers of PD as well as influence the protein aggregation behavior, structure, and cytotoxicity. Previous investigations show that some of the more common PTMs to the α-Syn secondary structures are phosphorylation of Tyr and Ser residues, Tyr oxidation leading to Tyr–Tyr cross-linking, nitration of Tyr residues, Lys modification (SUMOylation), transglutaminase cross-linking, truncation, N-terminus acetylation, and many others. Among the three different domains of α-Syn, it is the C-terminus region of the protein that hosts majority of the PTM sites. N-terminal and NAC regions also contain some PTM sites.…”
Section: Parkinson’s Disease (Pd)mentioning
confidence: 99%
“…As a result, certain disease-associated PTMs can potentially serve as biomarkers of PD as well as influence the protein aggregation behavior, structure, and cytotoxicity. Previous investigations show that some of the more common PTMs to the α-Syn secondary structures are phosphorylation of Tyr and Ser residues, Tyr oxidation leading to Tyr–Tyr cross-linking, nitration of Tyr residues, Lys modification (SUMOylation), transglutaminase cross-linking, truncation, N-terminus acetylation, and many others. Among the three different domains of α-Syn, it is the C-terminus region of the protein that hosts majority of the PTM sites. N-terminal and NAC regions also contain some PTM sites.…”
Section: Parkinson’s Disease (Pd)mentioning
confidence: 99%
“…Comparing the radii of gyration from a set of IDPs with experimental values showed only a slight tendency to favor compact conformations. This is particularly the case of α-synuclein, in which all-atom simulations have shown excellent agreement with experimental data. , This could point to some tendency to favor condensed states and left room for further improvements. Nevertheless, the general agreement with a theoretical polymer model underlined the correctness of the CG solvent model.…”
mentioning
confidence: 91%
“…15 Next, we investigated the impact of the PTM on the protein in its monomeric form and in the fibrils. Our investigation on monomeric AS here builds upon our AMBER-based Replica Exchange with Solute Tempering 2 (REST2) 16 enhanced sampling predictions of wild-type 17,18 and mutants 18 of the conformational ensemble of AS monomer in aqueous solution, in its physiological form 19 4 . The calculations are based on the two force fields tailored for IDPs.…”
Section: Introductionmentioning
confidence: 99%