Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the Aggregation
Parkinson’s disease (PD) is an increasingly prevalent and currently incurable neurodegenerative disorder. The aggregation of the amyloid disordered protein α-synuclein (Syn) has been implicated in the development of PD. In the literature, it has been suggested that tyrosine residues of Syn play an i...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Applied Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3417/12/7/3546 |
| _version_ | 1797440348704735232 |
|---|---|
| author | Marco A. Saraiva Maria Helena Florêncio |
| author_facet | Marco A. Saraiva Maria Helena Florêncio |
| author_sort | Marco A. Saraiva |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is an increasingly prevalent and currently incurable neurodegenerative disorder. The aggregation of the amyloid disordered protein α-synuclein (Syn) has been implicated in the development of PD. In the literature, it has been suggested that tyrosine residues of Syn play an important role in the interactions established during the fibrillation process. Herein, the prevalence of the referred interactions under shear stress conditions of <i>N</i><sub>α</sub>-acetyl-L-tyrosinamide (NAYA) and of Syn solutions by using membrane centrifugal filters with different cut-off of 200 nm, 100 kDa, 50 kDa and 30 kDa, under centrifugation conditions, were investigated. In order to determine the nature of the interactions involving the protein tyrosine residues the NAYA compound, which mimics the peptide bonds in protein and also possesses a tyrosyl group similar to the tyrosyl groups found in the Syn protein molecular structure, was used. It is expected that for a small molecule, such as NAYA, no molecular association occurs, contrary to what exists in the Syn protein solutions, which can more adequately retrieve the type of interactions formed, involving the tyrosyl group. Therefore, sensing the tyrosyl group absorption, spectroscopic techniques, in particular, were used. For NAYA, an intramolecular interaction between the tyrosyl group and the peptide bond was evidenced. For NAYA and Syn, it was observed that decreasing the membrane centrifugal filters pore size, under centrifugation conditions, was concomitant with the minimization of the intramolecular interactions between the tyrosyl group and the peptide bond. With this, it is likely to assume that shear stress conditions in the Syn solutions propel protein aggregation by a less strained protein backbone. Contrary to the centrifugation of NAYA solutions, centrifuging Syn solutions revealed molecular association and a progressive exposure of protein tyrosyl groups to water. Thus, we can also infer that shear stress conditions in the Syn solutions cause the protein tyrosyl groups to not intervene in the protein aggregation. |
| first_indexed | 2024-03-09T12:06:52Z |
| format | Article |
| id | doaj.art-9f82498ced7b4b69bacc20b48ff9527b |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-09T12:06:52Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-9f82498ced7b4b69bacc20b48ff9527b2023-11-30T22:57:13ZengMDPI AGApplied Sciences2076-34172022-03-01127354610.3390/app12073546Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the AggregationMarco A. Saraiva0Maria Helena Florêncio1Centro de Química Estrutural, Instituto Superior Técnico, Campus Alameda, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, PortugalDepartamento de Química e Bioquímica, Faculdade de Ciências, University of Lisbon, 1749-016 Lisbon, PortugalParkinson’s disease (PD) is an increasingly prevalent and currently incurable neurodegenerative disorder. The aggregation of the amyloid disordered protein α-synuclein (Syn) has been implicated in the development of PD. In the literature, it has been suggested that tyrosine residues of Syn play an important role in the interactions established during the fibrillation process. Herein, the prevalence of the referred interactions under shear stress conditions of <i>N</i><sub>α</sub>-acetyl-L-tyrosinamide (NAYA) and of Syn solutions by using membrane centrifugal filters with different cut-off of 200 nm, 100 kDa, 50 kDa and 30 kDa, under centrifugation conditions, were investigated. In order to determine the nature of the interactions involving the protein tyrosine residues the NAYA compound, which mimics the peptide bonds in protein and also possesses a tyrosyl group similar to the tyrosyl groups found in the Syn protein molecular structure, was used. It is expected that for a small molecule, such as NAYA, no molecular association occurs, contrary to what exists in the Syn protein solutions, which can more adequately retrieve the type of interactions formed, involving the tyrosyl group. Therefore, sensing the tyrosyl group absorption, spectroscopic techniques, in particular, were used. For NAYA, an intramolecular interaction between the tyrosyl group and the peptide bond was evidenced. For NAYA and Syn, it was observed that decreasing the membrane centrifugal filters pore size, under centrifugation conditions, was concomitant with the minimization of the intramolecular interactions between the tyrosyl group and the peptide bond. With this, it is likely to assume that shear stress conditions in the Syn solutions propel protein aggregation by a less strained protein backbone. Contrary to the centrifugation of NAYA solutions, centrifuging Syn solutions revealed molecular association and a progressive exposure of protein tyrosyl groups to water. Thus, we can also infer that shear stress conditions in the Syn solutions cause the protein tyrosyl groups to not intervene in the protein aggregation.https://www.mdpi.com/2076-3417/12/7/3546α-synucleinUV absorptiontyrosyl grouppeptide bondintramolecular/intermolecular interactions |
| spellingShingle | Marco A. Saraiva Maria Helena Florêncio Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the Aggregation Applied Sciences α-synuclein UV absorption tyrosyl group peptide bond intramolecular/intermolecular interactions |
| title | Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the Aggregation |
| title_full | Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the Aggregation |
| title_fullStr | Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the Aggregation |
| title_full_unstemmed | Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the Aggregation |
| title_short | Shear Stress Induces α-Synuclein Aggregation Due to a Less Strained Protein Backbone and Protein Tyrosyl Groups Do Not Intervene in the Aggregation |
| title_sort | shear stress induces α synuclein aggregation due to a less strained protein backbone and protein tyrosyl groups do not intervene in the aggregation |
| topic | α-synuclein UV absorption tyrosyl group peptide bond intramolecular/intermolecular interactions |
| url | https://www.mdpi.com/2076-3417/12/7/3546 |
| work_keys_str_mv | AT marcoasaraiva shearstressinducesasynucleinaggregationduetoalessstrainedproteinbackboneandproteintyrosylgroupsdonotinterveneintheaggregation AT mariahelenaflorencio shearstressinducesasynucleinaggregationduetoalessstrainedproteinbackboneandproteintyrosylgroupsdonotinterveneintheaggregation |