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oai:repisalud.isciii.es:20.500.12105/237962024-11-29T03:14:27Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967
Repisalud author Uceda, Ana Belén author Frau, Juan author Vilanova, Bartolomé author Adrover, Miquel 2024-10-09T06:36:32Z 2024-10-09T06:36:32Z 2023-06-20 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 (Basel, Switzerland). 2023 Jun 20;12(6). 10.3390/antiox12061310 2076-3921 Antioxidants (Basel, Switzerland) https://hdl.handle.net/20.500.13003/19079 37372040 https://hdl.handle.net/20.500.12105/23796 Parkinson's disease (PD) is characterized by dopaminergic neuron degeneration and the accumulation of neuronal inclusions known as Lewy bodies, which are formed by aggregated and post-translationally modified α-synuclein (αS). Oxidative modifications such as the formation of 3-nitrotyrosine (3-NT) or di-tyrosine are found in αS deposits, and they could be promoted by the oxidative stress typical of PD brains. Many studies have tried to elucidate the molecular mechanism correlating nitroxidation, αS aggregation, and PD. However, it is unclear how nitroxidation affects the physiological function of αS. To clarify this matter, we synthetized an αS with its Tyr residues replaced by 3-NT. Its study revealed that Tyr nitroxidation had no effect on either the affinity of αS towards anionic micelles nor the overall structure of the micelle-bound αS, which retained its α-helical folding. Nevertheless, we observed that nitroxidation of Y39 lengthened the disordered stretch bridging the two consecutive α-helices. Conversely, the affinity of αS towards synaptic-like vesicles diminished as a result of Tyr nitroxidation. Additionally, we also proved that nitroxidation precluded αS from performing its physiological function as a catalyst of the clustering and the fusion of synaptic vesicles. Our findings represent a step forward towards the completion of the puzzle that must explain the molecular mechanism behind the link between αS-nitroxidation and PD. eng 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 research article