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Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products

Protein dimerization via tyrosine residues is a crucial process in response to an oxidative attack, which has been identified in many ageing-related pathologies. Recently, it has been found that for isolated tyrosine amino acid, dimerization occurs through three types of tyrosine–tyrosine crosslinks...

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Autores principales: Gatin, Anouchka, Duchambon, Patricia, van der Rest, Guillaume, Billault, Isabelle, Sicard-Roselli, Cécile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835203/
https://www.ncbi.nlm.nih.gov/pubmed/35163094
http://dx.doi.org/10.3390/ijms23031174
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author Gatin, Anouchka
Duchambon, Patricia
van der Rest, Guillaume
Billault, Isabelle
Sicard-Roselli, Cécile
author_facet Gatin, Anouchka
Duchambon, Patricia
van der Rest, Guillaume
Billault, Isabelle
Sicard-Roselli, Cécile
author_sort Gatin, Anouchka
collection PubMed
description Protein dimerization via tyrosine residues is a crucial process in response to an oxidative attack, which has been identified in many ageing-related pathologies. Recently, it has been found that for isolated tyrosine amino acid, dimerization occurs through three types of tyrosine–tyrosine crosslinks and leads to at least four final products. Herein, considering two protected tyrosine residues, tyrosine-containing peptides and finally proteins, we investigate the dimerization behavior of tyrosine when embedded in a peptidic sequence. After azide radical oxidation and by combining UPLC-MS and H/D exchange analyzes, we were able to evidence: (i) the slow kinetics of Michael Addition Dimers (MAD) formation, i.e., more than 48 h; (ii) the co-existence of intermediates and final cyclized dimer products; and (iii) the probable involvement of amide functions to achieve Michael additions even in proteins. This raises the question of the possible in vivo existence of both intermediates and final entities as well as their toxicity and the potential consequences on protein structure and/or function.
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spelling pubmed-88352032022-02-12 Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products Gatin, Anouchka Duchambon, Patricia van der Rest, Guillaume Billault, Isabelle Sicard-Roselli, Cécile Int J Mol Sci Article Protein dimerization via tyrosine residues is a crucial process in response to an oxidative attack, which has been identified in many ageing-related pathologies. Recently, it has been found that for isolated tyrosine amino acid, dimerization occurs through three types of tyrosine–tyrosine crosslinks and leads to at least four final products. Herein, considering two protected tyrosine residues, tyrosine-containing peptides and finally proteins, we investigate the dimerization behavior of tyrosine when embedded in a peptidic sequence. After azide radical oxidation and by combining UPLC-MS and H/D exchange analyzes, we were able to evidence: (i) the slow kinetics of Michael Addition Dimers (MAD) formation, i.e., more than 48 h; (ii) the co-existence of intermediates and final cyclized dimer products; and (iii) the probable involvement of amide functions to achieve Michael additions even in proteins. This raises the question of the possible in vivo existence of both intermediates and final entities as well as their toxicity and the potential consequences on protein structure and/or function. MDPI 2022-01-21 /pmc/articles/PMC8835203/ /pubmed/35163094 http://dx.doi.org/10.3390/ijms23031174 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Gatin, Anouchka
Duchambon, Patricia
van der Rest, Guillaume
Billault, Isabelle
Sicard-Roselli, Cécile
Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products
title Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products
title_full Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products
title_fullStr Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products
title_full_unstemmed Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products
title_short Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products
title_sort protein dimerization via tyr residues: highlight of a slow process with co-existence of numerous intermediates and final products
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835203/
https://www.ncbi.nlm.nih.gov/pubmed/35163094
http://dx.doi.org/10.3390/ijms23031174
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