Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulation
Pathological aggregation of essentially dissociative Transthyretin (TTR) monomers protein, driven by misfolded and self-interaction, is connected with Amyloid Transthyretin amyloidosis (ATTR) disease. The TTR monomers protein contains several fragments that tend to self-aggregate, such as residue 10...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.982276/full |
| _version_ | 1817999087554789376 |
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| author | Yuqi Zhang Yanyan Zhu Haiyan Yue Qingjie Zhao Huiyu Li |
| author_facet | Yuqi Zhang Yanyan Zhu Haiyan Yue Qingjie Zhao Huiyu Li |
| author_sort | Yuqi Zhang |
| collection | DOAJ |
| description | Pathological aggregation of essentially dissociative Transthyretin (TTR) monomers protein, driven by misfolded and self-interaction, is connected with Amyloid Transthyretin amyloidosis (ATTR) disease. The TTR monomers protein contains several fragments that tend to self-aggregate, such as residue 105–115 sequence [TTR (105–115)]. However, the misfolding and aggregation mechanisms of TTR are still unknown. In this study, we explored the misfolding and self-assembly of TTR (105–115) peptides by all-atom molecular dynamics simulation. Our results indicated that the conformation of the two-peptides appears unstable. In the tetramerization and hexamerization simulations, the results are reversed. When the number of peptides increases, the probability and the length of β-Sheet contents increase. Our results show that that the four- and six-peptides both can form β-Barrel intermediates and then aggregate into fibers. The critical nucleation for the formation of fibril should be larger than four-peptides. The interactions between hydrophobic residues I107-L111 play an important role in the formation of stable fibrils at an early stage. Our results on the structural ensembles and early aggregation dynamics of TTR (105–115) will be useful to comprehend the nucleation and fibrillization of TTR (105–115). |
| first_indexed | 2024-04-14T03:03:19Z |
| format | Article |
| id | doaj.art-0a49e37e5d514268b70cf5a3d7f0609a |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-14T03:03:19Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-0a49e37e5d514268b70cf5a3d7f0609a2022-12-22T02:15:49ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-08-01910.3389/fmolb.2022.982276982276Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulationYuqi Zhang0Yanyan Zhu1Haiyan Yue2Qingjie Zhao3Huiyu Li4College of Mathematics and Physics, Shanghai University of Electric Power, Shanghai, ChinaCollege of Mathematics and Physics, Shanghai University of Electric Power, Shanghai, ChinaNaval Medical Center of PLA, Department of Digestive Diseases, Naval Medical University, Shanghai, ChinaInnovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCollege of Mathematics and Physics, Shanghai University of Electric Power, Shanghai, ChinaPathological aggregation of essentially dissociative Transthyretin (TTR) monomers protein, driven by misfolded and self-interaction, is connected with Amyloid Transthyretin amyloidosis (ATTR) disease. The TTR monomers protein contains several fragments that tend to self-aggregate, such as residue 105–115 sequence [TTR (105–115)]. However, the misfolding and aggregation mechanisms of TTR are still unknown. In this study, we explored the misfolding and self-assembly of TTR (105–115) peptides by all-atom molecular dynamics simulation. Our results indicated that the conformation of the two-peptides appears unstable. In the tetramerization and hexamerization simulations, the results are reversed. When the number of peptides increases, the probability and the length of β-Sheet contents increase. Our results show that that the four- and six-peptides both can form β-Barrel intermediates and then aggregate into fibers. The critical nucleation for the formation of fibril should be larger than four-peptides. The interactions between hydrophobic residues I107-L111 play an important role in the formation of stable fibrils at an early stage. Our results on the structural ensembles and early aggregation dynamics of TTR (105–115) will be useful to comprehend the nucleation and fibrillization of TTR (105–115).https://www.frontiersin.org/articles/10.3389/fmolb.2022.982276/fullTTR(105–115)peptide aggregationβ-Barrelhydrophobic interactionmolecular dynamics simulationATTR |
| spellingShingle | Yuqi Zhang Yanyan Zhu Haiyan Yue Qingjie Zhao Huiyu Li Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulation Frontiers in Molecular Biosciences TTR(105–115) peptide aggregation β-Barrel hydrophobic interaction molecular dynamics simulation ATTR |
| title | Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulation |
| title_full | Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulation |
| title_fullStr | Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulation |
| title_full_unstemmed | Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulation |
| title_short | Exploring the misfolding and self-assembly mechanism of TTR (105–115) peptides by all-atom molecular dynamics simulation |
| title_sort | exploring the misfolding and self assembly mechanism of ttr 105 115 peptides by all atom molecular dynamics simulation |
| topic | TTR(105–115) peptide aggregation β-Barrel hydrophobic interaction molecular dynamics simulation ATTR |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.982276/full |
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