Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis
Abstract
:1. Introduction
2. Results
2.1. Thymosin β4 Metal Coordination
2.2. Thymosin β4 and Ferroptosis
3. Discussion
4. Conclusions
5. Experimental Procedures
5.1. Reagents
5.2. EPR Experimental Details
5.3. NMR
5.4. DFT
System Setup and Conformational Analysis
5.5. Molecular Dynamics Simulations
5.6. Cell Cultures
5.7. Cell Viability Measurements
5.8. Gene Expression
5.9. TEM Microscopy
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Binding Region | I | II | III | IV | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Fe (II) | S1 | K3 | P4 | - | M6 | - | - | K11 | F12 | D13 | S15 | L17 | T22 | P27 | L28 | P29 | S30 | T33 | I34 | - | - | A40 | S43 |
Fe (III) | S1 | K3 | P4 | - | M6 | I9 | - | - | F12 | D13 | S15 | - | T22 | - | L28 | - | - | T33 | I34 | Q35 | E36 | A40 | - |
Al (III) | - | - | P4 | D5 | M6 | I9 | E10 | - | F12 | D13 | - | - | - | - | L28 | - | - | - | I34 | Q35 | E36 | - | - |
TB4N-C | TB4N-mid | TB4N-N | ||||||
---|---|---|---|---|---|---|---|---|
Donor | Acceptor | Occ. (%) | Donor | Acceptor | Occ. (%) | Donor | Acceptor | Occ. (%) |
GLU35-Nbb | THR33-Osc | 27.6 | LYS38-Nbb | GLU35-Obb | 26.0 | THR22-Nbb | LYS19-Obb | 23.8 |
LEU17-Nbb | LYS14-Obb | 25.8 | LEU28-Nbb | ASN26-Osc | 28.2 | GLN23-Nbb | LYS18-Obb | 22.2 |
LEU28-Nbb | ASN26-Osc | 36.6 | ILE34-Nbb | LYS31-Obb | 26.7 | GLU21-Nbb | LEU17-Obb | 23.4 |
THR33-Nbb | GLN36-Obb | 32.0 | LYS31-Nbb | LEU28-Obb | 21.1 | ILE9-Nbb | MET6-Obb | 53.0 |
LYS31-Nbb | LEU28-Obb | 22.5 | - | - | - | GLU8-Nbb | ASP5-Obb | 51.5 |
- | - | - | - | - | - | LYS38-Nbb | GLU35-Obb | 20.0 |
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Lachowicz, J.I.; Pichiri, G.; Piludu, M.; Fais, S.; Orrù, G.; Congiu, T.; Piras, M.; Faa, G.; Fanni, D.; Dalla Torre, G.; et al. Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis. Int. J. Mol. Sci. 2022, 23, 551. https://doi.org/10.3390/ijms23010551
Lachowicz JI, Pichiri G, Piludu M, Fais S, Orrù G, Congiu T, Piras M, Faa G, Fanni D, Dalla Torre G, et al. Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis. International Journal of Molecular Sciences. 2022; 23(1):551. https://doi.org/10.3390/ijms23010551
Chicago/Turabian StyleLachowicz, Joanna I., Giusi Pichiri, Marco Piludu, Sara Fais, Germano Orrù, Terenzio Congiu, Monica Piras, Gavino Faa, Daniela Fanni, Gabriele Dalla Torre, and et al. 2022. "Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis" International Journal of Molecular Sciences 23, no. 1: 551. https://doi.org/10.3390/ijms23010551