Conformational Changes and Unfolding of β-Amyloid Substrates in the Active Site of γ-Secretase
Abstract
:1. Introduction
2. Results and Discussion
3. Methods and Materials
3.1. Preparation of the Structure
3.2. Molecular Dynamics (MD) Simulations
3.3. Steered Molecular Dynamics (SMD) Simulations
3.4. Statistical Procedure and the Box-Plot
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Mutation | Biological Effect | Ref. |
---|---|---|
R269G | Early-onset AD; decreased protease activity with APP; increased Aβ42/Aβ40 ratio. | [30] |
R269H | Early-onset AD; increased Aβ (42 + 43)/(37 + 38 + 40) ratio in cells; decreased GS activity. | [29,31,32] |
R377M | Early-onset AD; uncertain significance, but in silico algorithm predicted it is deleterious. | [29] |
R377W | In vitro, decreased Aβ42 production and abrogated Aβ40 production; nearly abolishes protease activity with APP. | [30,33,34] |
K380R | Unknown, but in silico predictions suggest damaging effect. | [32] |
Del377-381 | Loss of Notch1 and APP-C83 cleavage. | [18,28] |
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Jakowiecki, J.; Orzeł, U.; Miszta, P.; Młynarczyk, K.; Filipek, S. Conformational Changes and Unfolding of β-Amyloid Substrates in the Active Site of γ-Secretase. Int. J. Mol. Sci. 2024, 25, 2564. https://doi.org/10.3390/ijms25052564
Jakowiecki J, Orzeł U, Miszta P, Młynarczyk K, Filipek S. Conformational Changes and Unfolding of β-Amyloid Substrates in the Active Site of γ-Secretase. International Journal of Molecular Sciences. 2024; 25(5):2564. https://doi.org/10.3390/ijms25052564
Chicago/Turabian StyleJakowiecki, Jakub, Urszula Orzeł, Przemysław Miszta, Krzysztof Młynarczyk, and Sławomir Filipek. 2024. "Conformational Changes and Unfolding of β-Amyloid Substrates in the Active Site of γ-Secretase" International Journal of Molecular Sciences 25, no. 5: 2564. https://doi.org/10.3390/ijms25052564