Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Expression and Purification of Human α-Synuclein
2.3. Synthesis of Nitroxidated α-Synuclein (αS-NO2)
2.4. Small Unilamellar Vesicles’ Preparation
2.5. Circular Dichroism Spectroscopy
2.6. NMR Spectroscopy Measurements
2.7. NMR Assignment of αS-NO2 Bound to SDS Micelles
2.8. NMR Structure Calculations
2.9. NMR Relaxation Measurements
2.10. Determination of the Dissociation Constant of the ESC-SUV-Bound αS-NO2
2.11. Dynamic Light Scattering Measurements
2.12. Fluorescence Anisotropy
2.13. Calcein Release Assay
3. Results
3.1. Obtaining a Homogeneously Nitroxidated αS
3.2. Tyr Nitroxidation Hinders the SUV-Induced α-Helical Folding of αS, but It Does Not Have Any Effect on the SDS-Micelle-Induced α-Helical Folding of αS
3.3. Tyr Nitroxidation Has No Effect on αS Affinity towards SDS-Micelles
3.4. Tyr Nitroxidation Diminishes the Affinity of αS towards SUVs
3.5. Nitroxidation of Y39 Lengthens the Disordered Linker Connecting the Two Antiparallel α-Helices of the Micelle-Bound αS
3.6. Tyr Nitroxidation Does Not Affect the Dynamics of the Micelle-Bound αS
3.7. The Ability of αS to Increase the Lipid Bilayer Ordering Is Not Affected by Tyr Nitroxidation
3.8. Tyr Nitroxidation of αS Has No Effect on the Membrane Integrity of SUVs
3.9. Tyr Nitroxidation Abolishes the Ability of αS to Induce SUV Fusion
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Maroteaux, L.; Campanelli, J.T.; Scheller, R.H. Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 1998, 8, 2804–2815. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lashuel, H.A.; Overk, C.R.; Oueslati, A.; Masliah, E. The many faces of α-synuclein: From structure and toxicity to therapeutic target. Nat. Rev. Neurosci. 2013, 14, 38–48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murphy, D.D.; Rueter, S.M.; Trojanowski, J.Q.; Lee, V.M. Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J. Neurosci. 2000, 20, 3214–3220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Scott, D.A.; Tabarean, I.; Tang, Y.; Cartier, A.; Masliah, E.; Roy, S. A pathologic cascade leading to synaptic dysfunction in alpha-synuclein-induced neurodegeneration. J. Neurosci. 2010, 30, 8083–8095. [Google Scholar] [CrossRef] [Green Version]
- Nemani, V.M.; Lu, W.; Berge, V.; Nakamura, K.; Onoa, B.; Lee, M.K.; Chaudhry, F.A.; Nicoll, R.A.; Edwards, R.H. Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 2010, 65, 66–79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Emamzadeh, F.N. Alpha-synuclein structure; functions; and interactions. J. Res. Med. Sci. 2016, 21, 29. [Google Scholar] [CrossRef] [PubMed]
- Theillet, F.X.; Binolfi, A.; Bekei, B.; Martorana, A.; Rose, H.M.; Stuiver, M.; Verzini, S.; Lorenz, D.; van Rossum, M.; Goldfarb, D.; et al. Structural disorder of monomeric α-synuclein persists in mammalian cells. Nature 2016, 530, 45–50. [Google Scholar] [CrossRef] [Green Version]
- Ulmer, T.S.; Bax, A.; Cole, N.B.; Nussbaum, R.L. Structure and dynamics of micelle-bound human alpha-synuclein. J. Biol. Chem. 2005, 280, 9595–9603. [Google Scholar] [CrossRef] [Green Version]
- Fusco, G.; Sanz-Hernandez, M.; De Simone, A. Order and disorder in the physiological membrane binding of α-synuclein. Curr. Opin. Struct. Biol. 2018, 48, 49–57. [Google Scholar] [CrossRef]
- Chandra, S.; Chen, X.; Rizo, J.; Jahn, R.; Südhof, T.C. A broken alpha-helix in folded alpha-Synuclein. J. Biol. Chem. 2003, 278, 15313–15318. [Google Scholar] [CrossRef] [Green Version]
- Uceda, A.B.; Frau, J.; Vilanova, B.; Adrover, M. Glycation of α-synuclein hampers its binding to synaptic-like vesicles and its driving effect on their fusion. Cell. Mol. Life Sci. 2022, 79, 342. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.J.; Choi, C.; Lee, S.J. Membrane-bound alpha-synuclein has a high aggregation propensity and the ability to seed the aggregation of the cytosolic form. J. Biol. Chem. 2002, 277, 671–678. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Davidson, W.S.; Jonas, A.; Clayton, D.F.; George, J.M. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 1998, 273, 9443–9449. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Middleton, E.R.; Rhoades, E. Effects of curvature and composition on α-synuclein binding to lipid vesicles. Biophys. J. 2010, 99, 2279–2288. [Google Scholar] [CrossRef] [Green Version]
- Zarbiv, Y.; Simhi-Haham, D.; Israeli, E.; Elhadi, S.A.; Grigoletto, J.; Sharon, R. Lysine residues at the first and second KTKEGV repeats mediate α-Synuclein binding to membrane phospholipids. Neurobiol. Dis. 2014, 70, 90–98. [Google Scholar] [CrossRef]
- Pirc, K.; Ulrih, N.P. α-Synuclein interactions with phospholipid model membranes: Key roles for electrostatic interactions and lipid-bilayer structure. Biochim. Biophys. Acta 2015, 1848, 2002–2012. [Google Scholar] [CrossRef] [Green Version]
- Takamori, S.; Holt, M.; Stenius, K.; Lemke, E.A.; Grønborg, M.; Riedel, D.; Urlaub, H.; Schenck, S.; Brügger, B.; Ringler, P.; et al. Molecular anatomy of a trafficking organelle. Cell 2006, 127, 831–846. [Google Scholar] [CrossRef] [Green Version]
- Pfefferkorn, C.M.; Jiang, Z.; Lee, J.C. Biophysics of α-synuclein membrane interactions. Biochim. Biophys. Acta 2012, 1818, 162–171. [Google Scholar] [CrossRef] [Green Version]
- Cui, H.; Lyman, E.; Voth, G.A. Mechanism of membrane curvature sensing by amphipathic helix containing proteins. Biophys. J. 2011, 100, 1271–1279. [Google Scholar] [CrossRef] [Green Version]
- Spillantini, M.G.; Schmidt, M.L.; Lee, V.M.; Trojanowski, J.Q.; Jakes, R.; Goedert, M. Alpha-synuclein in Lewy bodies. Nature 1997, 388, 839–840. [Google Scholar] [CrossRef]
- Shults, C.W. Lewy bodies. Proc. Natl. Acad. Sci. USA 2006, 103, 1661–1668. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ugalde, C.L.; Lawson, V.A.; Finkelstein, D.I.; Hill, A.F. The role of lipids in α-synuclein misfolding and neurotoxicity. J. Biol. Chem. 2019, 294, 9016–9028. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ghosh, D.; Mehra, S.; Sahay, S.; Singh, P.K.; Maji, S.K. α-synuclein aggregation and its modulation. Int. J. Biol. Macromol. 2017, 100, 37–54. [Google Scholar] [CrossRef]
- Galvagnion, C.; Buell, A.K.; Meisl, G.; Michaels, T.C.; Vendruscolo, M.; Knowles, T.P.; Dobson, C.M. Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation. Nat. Chem. Biol. 2015, 11, 229–234. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhu, M.; Li, J.; Fink, A.L. The association of alpha-synuclein with membranes affects bilayer structure; stability; and fibril formation. J. Biol. Chem. 2003, 278, 40186–40197. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, J.; Li, X.; Li, J.D. The Roles of Post-translational Modifications on α-Synuclein in the Pathogenesis of Parkinson’s Diseases. Front. Neurosci. 2019, 13, 381. [Google Scholar] [CrossRef] [Green Version]
- Mariño, L.; Ramis, R.; Casasnovas, R.; Ortega-Castro, J.; Vilanova, B.; Frau, J.; Adrover, M. Unravelling the effect of Nε-(carboxyethyl)lysine on the conformation; dynamics and aggregation propensity of α-synuclein. Chem. Sci. 2020, 11, 3332–3344. [Google Scholar] [CrossRef] [Green Version]
- Uceda, A.B.; Frau, J.; Vilanova, B.; Adrover, M. On the effect of methionine oxidation on the interplay between α-synuclein and synaptic-like vesicles. Int. J. Biol. Macromol. 2023, 229, 92–104. [Google Scholar] [CrossRef]
- Glaser, C.B.; Yamin, G.; Uversky, V.N.; Fink, A.L. Methionine oxidation; alpha-synuclein and Parkinson’s disease. Biochim. Biophys. Acta 2005, 1703, 157–169. [Google Scholar] [CrossRef]
- Fujiwara, H.; Hasegawa, M.; Dohmae, N.; Kawashima, A.; Masliah, E.; Goldberg, M.S.; Shen, J.; Takio, K.; Iwatsubo, T. Alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol. 2002, 4, 160–164. [Google Scholar] [CrossRef]
- McCormack, A.L.; Mak, S.K.; Di Monte, D.A. Increased α-synuclein phosphorylation and nitration in the aging primate substantia nigra. Cell Death Dis. 2012, 3, e315. [Google Scholar] [CrossRef] [Green Version]
- Schildknecht, S.; Gerding, H.R.; Karreman, C.; Drescher, M.; Lashuel, H.A.; Outeiro, T.F.; Di Monte, D.A.; Leist, M. Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: Implications for disease mechanisms and interventions in synucleinopathies. J. Neurochem. 2013, 125, 491–511. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beckman, J.S.; Crow, J.P. Pathological implications of nitric oxide; superoxide and peroxynitrite formation. Biochem. Soc. Trans. 1993, 21, 330–334. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Radi, R. Nitric oxide; oxidants; and protein tyrosine nitration. Proc. Natl. Acad. Sci. USA 2004, 101, 4003–4008. [Google Scholar] [CrossRef] [Green Version]
- Prigione, A.; Piazza, F.; Brighina, L.; Begni, B.; Galbussera, A.; Difrancesco, J.C.; Andreoni, S.; Piolti, R.; Ferrarese, C. Alpha-synuclein nitration and autophagy response are induced in peripheral blood cells from patients with Parkinson disease. Neurosci. Lett. 2010, 477, 6–10. [Google Scholar] [CrossRef]
- Giasson, B.I.; Duda, J.E.; Murray, I.V.; Chen, Q.; Souza, J.M.; Hurtig, H.I.; Ischiropoulos, H.; Trojanowski, J.Q.; Lee, V.M. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 2000, 290, 985–989. [Google Scholar] [CrossRef] [PubMed]
- Yu, Z.; Xu, X.; Xiang, Z.; Zhou, J.; Zhang, Z.; Hu, C.; He, C. Nitrated alpha-synuclein induces the loss of dopaminergic neurons in the substantia nigra of rats. PLoS ONE 2010, 5, e9956. [Google Scholar] [CrossRef]
- Souza, J.M.; Giasson, B.I.; Chen, Q.; Lee, V.M.; Ischiropoulos, H. Dityrosine cross-linking promotes formation of stable alpha -synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J. Biol. Chem. 2000, 275, 18344–18349. [Google Scholar] [CrossRef] [Green Version]
- Hodara, R.; Norris, E.H.; Giasson, B.I.; Mishizen-Eberz, A.J.; Lynch, D.R.; Lee, V.M.; Ischiropoulos, H. Functional consequences of alpha-synuclein tyrosine nitration: Diminished binding to lipid vesicles and increased fibril formation. J. Biol. Chem. 2004, 279, 47746–47753. [Google Scholar] [CrossRef] [Green Version]
- Sevcsik, E.; Trexler, A.J.; Dunn, J.M.; Rhoades, E. Allostery in a disordered protein: Oxidative modifications to α-synuclein act distally to regulate membrane binding. J. Am. Chem. Soc. 2011, 133, 7152–7158. [Google Scholar] [CrossRef] [Green Version]
- Martínez-Orozco, H.; Mariño, L.; Uceda, A.B.; Ortega-Castro, J.; Vilanova, B.; Frau, J.; Adrover, M. Nitration and Glycation Diminish the α-Synuclein Role in the Formation and Scavenging of Cu2+-Catalyzed Reactive Oxygen Species. ACS Chem. Neurosci. 2019, 10, 2919–2930. [Google Scholar] [CrossRef] [PubMed]
- Stewart, J.C. Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal. Biochem. 1980, 104, 10–14. [Google Scholar] [CrossRef]
- Scholtz, J.M.; Qian, H.; York, E.J.; Stewart, J.M.; Baldwin, R.L. Parameters of helix-coil transition theory for alanine-based peptides of varying chain lengths in water. Biopolymers 1991, 31, 1463–1470. [Google Scholar] [CrossRef] [Green Version]
- Piotto, M.; Saudek, V.; Sklenár, V.J. Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J. Biomol. NMR 1992, 2, 661–667. [Google Scholar] [CrossRef]
- Wishart, D.S.; Bigam, C.G.; Yao, J.; Abildgaard, F.; Dyson, H.J.; Oldfield, E.; Markley, J.L.; Sykes, B.D. 1H; 13C and 15N chemical shift referencing in biomolecular NMR. J. Biomol. NMR 1995, 6, 135–140. [Google Scholar] [CrossRef] [PubMed]
- Delaglio, F.; Grzesiek, S.; Vuister, G.; Zhu, G.; Pfeifer, J.; Bax, A. NMRPipe: A multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 1995, 6, 277–293. [Google Scholar] [CrossRef]
- Tamiola, K.; Mulder, F.A. Using NMR chemical shifts to calculate the propensity for structural order and disorder in proteins. Biochem. Soc. Trans. 2012, 40, 1014–1020. [Google Scholar] [CrossRef] [Green Version]
- Hafsa, N.E.; Arndt, D.; Wishart, D.S. CSI 3.0: A web server for identifying secondary and super-secondary structure in proteins using NMR chemical shifts. Nucleic Acids Res. 2015, 43, W370–W377. [Google Scholar] [CrossRef] [Green Version]
- Shen, Y.; Delaglio, F.; Cornilescu, G.; Bax, A. TALOS+: A hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J. Biomol. NMR 2009, 44, 213–223. [Google Scholar] [CrossRef] [PubMed]
- Lee, W.; Stark, J.L.; Markley, J.L. PONDEROSA-C/S: Client–server based software package for automated protein 3D structure determination. J. Biomol. NMR 2014, 60, 73–75. [Google Scholar] [CrossRef] [Green Version]
- Berjanskii, M.V.; Neal, S.; Wishart, D.S. PREDITOR: A web server for predicting protein torsion angle restraints. Nucleic Acids Res. 2016, 34, W63–W69. [Google Scholar] [CrossRef] [Green Version]
- Lee, W.; Petit, C.M.; Cornilescu, G.; Stark, J.L.; Markley, J.L. The AUDANA algorithm for automated protein 3D structure determination from NMR NOE data. J. Biomol. NMR 2016, 65, 51–57. [Google Scholar] [CrossRef] [Green Version]
- Laskowski, R.A.; Rullmann, J.A.; MacArthur, M.W.; Kaptein, R.; Thornton, J.M. AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR. J. Biomol. NMR 1996, 8, 447–486. [Google Scholar] [CrossRef] [PubMed]
- Farrow, N.A.; Muhandiram, R.; Singer, A.U.; Pascal, S.M.; Kay, C.M.; Gish, G.; Shoelson, S.E.; Pawson, T.; Forman-Kay, J.D.; Kay, L.E. Backbone dynamics of a free and phosphopeptide-complexed Src homology 2 domain studied by 15N NMR relaxation. Biochemistry 1994, 33, 5984–6003. [Google Scholar] [CrossRef]
- Dikiy, I.; Fauvet, B.; Jovičić, A.; Mahul-Mellier, A.L.; Desobry, C.; El-Turk, F.; Gitler, A.D.; Lashuel, H.A.; Eliezer, D. Semisynthetic and in Vitro Phosphorylation of Alpha-Synuclein at Y39 Promotes Functional Partly Helical Membrane-Bound States Resembling Those Induced by PD Mutations. ACS Chem. Biol. 2016, 11, 2428–2437. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zigoneanu, I.G.; Yang, Y.J.; Krois, A.S.; Haque, E.; Pielak, G.J. Interaction of α-synuclein with vesicles that mimic mitochondrial membranes. Biochim. Biophys. Acta 2012, 1818, 512–519. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lakowicz, J. Principles of Fluorescence Spectroscopy; Springer: Boston, MA, USA, 2006. [Google Scholar]
- Fisher, P.B.; Schachter, D.; Abbott, E.R.; Callaham, M.F.; Huberman, E. Membrane Lipid Dynamics in Human Promyelocytic Leukemia Cells Sensitive and Resistant to 12-O-Tetradecanoylphorbol-13-acetate Induction of Differentiation. Cancer Res. 1984, 44, 5550–5554. [Google Scholar]
- Dutta, S.; Watson, B.G.; Mattoo, S.; Rochet, J.C. Calcein Release Assay to Measure Membrane Permeabilization by Recombinant Alpha-Synuclein. Bio Protoc. 2020, 10, e3690. [Google Scholar] [CrossRef]
- De Filippis, V.; Frasson, R.; Fontana, A. 3-Nitrotyrosine as a spectroscopic probe for investigating protein protein interactions. Protein Sci. 2006, 15, 976–986. [Google Scholar] [CrossRef] [Green Version]
- Sokolovsky, M.; Riordan, J.F.; Vallee, B.L. Tetranitromethane. A reagent for the nitration of tyrosyl residues in proteins. Biochemistry 1996, 5, 3582–3589. [Google Scholar] [CrossRef]
- Burai, R.; Ait-Bouziad, N.; Chiki, A.; Lashuel, H.A. Elucidating the Role of Site-Specific Nitration of α-Synuclein in the Pathogenesis of Parkinson’s Disease via Protein Semisynthesis and Mutagenesis. J. Am. Chem. Soc. 2015, 137, 5041–5052. [Google Scholar] [CrossRef] [PubMed]
- Yamin, G.; Uversky, V.N.; Fink, A.L. Nitration inhibits fibrillation of human alpha-synuclein in vitro by formation of soluble oligomers. FEBS Lett. 2003, 542, 147–152. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, C.; Zhao, C.; Li, D.; Tian, Z.; Lai, Y.; Diao, J.; Liu, C. Versatile Structures of α-Synuclein. Front. Mol. Neurosci. 2016, 9, 48. [Google Scholar] [CrossRef]
- Bodner, C.R.; Dobson, C.M.; Bax, A. Multiple tight phospholipid-binding modes of alpha-synuclein revealed by solution NMR spectroscopy. J. Mol. Biol. 2009, 390, 775–790. [Google Scholar] [CrossRef] [Green Version]
- Maltsev, A.S.; Chen, J.; Levine, R.L.; Bax, A. Site-specific interaction between α-synuclein and membranes probed by NMR-observed methionine oxidation rates. J. Am. Chem. Soc. 2013, 135, 2943–2946. [Google Scholar] [CrossRef]
- Ouberai, M.M.; Wang, J.; Swann, M.J.; Galvagnion, C.; Guilliams, T.; Dobson, C.M.; Welland, M.E. α-Synuclein senses lipid packing defects and induces lateral expansion of lipids leading to membrane remodeling. J. Biol. Chem. 2013, 288, 20883–20895. [Google Scholar] [CrossRef] [Green Version]
- Fusco, G.; Pape, T.; Stephens, A.D.; Mahou, P.; Costa, A.R.; Kaminski, C.F.; Kaminski Schierle, G.S.; Vendruscolo, M.; Veglia, G.; Dobson, C.M.; et al. Structural basis of synaptic vesicle assembly promoted by α-synuclein. Nat. Commun. 2016, 7, 12563. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Croke, R.L.; Sallum, C.O.; Watson, E.; Watt, E.D.; Alexandrescu, A.T. Hydrogen exchange of monomeric alpha-synuclein shows unfolded structure persists at physiological temperature and is independent of molecular crowding in Escherichia coli. Protein Sci. 2008, 17, 1434–1445. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eliezer, D.; Kutluay, E.; Bussell, R., Jr.; Browne, G. Conformational properties of alpha-synuclein in its free and lipid-associated states. J. Mol. Biol. 2001, 307, 1061–1073. [Google Scholar] [CrossRef] [PubMed]
- Perlmutter, J.D.; Braun, A.R.; Sachs, J.N. Curvature dynamics of α-Synuclein familial Parkinson disease mutants. Molecular simulations of the Micelle-and Bilayer-bound forms. J. Biol. Chem. 2009, 284, 7177–7189. [Google Scholar] [CrossRef] [Green Version]
- Van Rooijen, B.D.; Claessens, M.M.A.E. Lipid bilayer disruption by oligomeric alpha-synuclein depends on bilayer charge and accessibility of the hydrophobic core. Biochim. Biophys. Acta 2009, 1788, 1271–1278. [Google Scholar] [CrossRef] [Green Version]
- Barnham, K.J.; Masters, C.L.; Bush, A.I. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov. 2004, 3, 205–214. [Google Scholar] [CrossRef]
- Blesa, J.; Trigo-Damas, I.; Quiroga-Varela, A.; Jackson-Lewis, V.R. Oxidative stress and Parkinson’s disease. Front. Neuroanat. 2015, 9, 91. [Google Scholar] [CrossRef] [Green Version]
- Chavarría, C.; Souza, J.M. Oxidation and nitration of α-synuclein and their implications in neurodegenerative diseases. Arch. Biochem. Biophys. 2013, 533, 25–32. [Google Scholar] [CrossRef] [PubMed]
- Duda, J.E.; Giasson, B.I.; Chen, Q.; Gur, T.L.; Hurtig, H.I.; Stern, M.B.; Gollomp, S.M.; Ischiropoulos, H.; Lee, V.M.; Trojanowski, J.Q. Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am. J. Pathol. 2000, 157, 1439–1445. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernandez, E.; Garcia-Moreno, J.M.; Martin de Pablos, A.; Chacon, J. May the evaluation of nitrosative stress through selective increase of 3-nitrotyrosine proteins other than nitroalbumin and dominant tyrosine-125/136 nitrosylation of serum α-synuclein serve for diagnosis of sporadic Parkinson’s disease? Antioxid. Redox Signal. 2013, 19, 912–918. [Google Scholar] [CrossRef] [Green Version]
- Reynolds, A.D.; Glanzer, J.G.; Kadiu, I.; Ricardo-Dukelow, M.; Chaudhuri, A.; Ciborowski, P.; Cerny, R.; Gelman, B.; Thomas, M.P.; Mosley, R.L.; et al. Nitrated alpha-synuclein-activated microglial profiling for Parkinson’s disease. J. Neurochem. 2008, 104, 1504–1525. [Google Scholar] [CrossRef] [Green Version]
- Martinez-Vicente, M.; Talloczy, Z.; Kaushik, S.; Massey, A.C.; Mazzulli, J.; Mosharov, E.V.; Hodara, R.; Fredenburg, R.; Wu, D.C.; Follenzi, A.; et al. Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J. Clin. Investig. 2008, 118, 777–788. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Uversky, V.N.; Yamin, G.; Munishkina, L.A.; Karymov, M.A.; Millett, I.S.; Doniach, S.; Lyubchenko, Y.L.; Fink, A.L. Effects of nitration on the structure and aggregation of alpha-synuclein. Brain Res. Mol. Brain Res. 2005, 134, 84–102. [Google Scholar] [CrossRef] [PubMed]
- Choi, Y.G.; Lim, S. Nɛ-(carboxymethyl)lysine linkage to α-synuclein and involvement of advanced glycation end products in α-synuclein deposits in an MPTP-intoxicated mouse model. Biochimie 2010, 92, 1379–1386. [Google Scholar] [CrossRef]
- Tessari, I.; Bisaglia, M.; Valle, F.; Samorì, B.; Bergantino, E.; Mammi, S.; Bubacco, L. The reaction of alpha-synuclein with tyrosinase: Possible implications for Parkinson disease. J. Biol. Chem. 2008, 283, 16808–16817. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lange, O.F.; Rossi, P.; Sgourakis, N.G.; Song, Y.; Lee, H.W.; Aramini, J.M.; Ertekin, A.; Xiao, R.; Acton, T.B.; Montelione, G.T.; et al. Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples. Proc. Natl. Acad. Sci. USA 2012, 109, 10873–10878. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhattacharya, A.; Tejero, R.; Montelione, G.T. Evaluating protein structures determined by structural genomics consortia. Proteins 2007, 66, 778–795. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Uceda, A.B.; Frau, J.; Vilanova, B.; Adrover, M. Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles. Antioxidants 2023, 12, 1310. https://doi.org/10.3390/antiox12061310
Uceda AB, Frau J, Vilanova B, Adrover M. Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles. Antioxidants. 2023; 12(6):1310. https://doi.org/10.3390/antiox12061310
Chicago/Turabian StyleUceda, Ana Belén, Juan Frau, Bartolomé Vilanova, and Miquel Adrover. 2023. "Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles" Antioxidants 12, no. 6: 1310. https://doi.org/10.3390/antiox12061310
APA StyleUceda, A. B., Frau, J., Vilanova, B., & Adrover, M. (2023). Tyrosine Nitroxidation Does Not Affect the Ability of α-Synuclein to Bind Anionic Micelles, but It Diminishes Its Ability to Bind and Assemble Synaptic-like Vesicles. Antioxidants, 12(6), 1310. https://doi.org/10.3390/antiox12061310