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Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains

The current belief is that amino acid sequences in protein structures are defined by DNA sequences. I challenge this concept by hypothesizing that an arginine (Arg) residue in the protein structure can post-translationally be converted to a proline (Pro) residue through a redox mechanism. Reactive o...

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Autor principal: Suzuki, Yuichiro Justin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318405/
https://www.ncbi.nlm.nih.gov/pubmed/35888057
http://dx.doi.org/10.3390/life12070967
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author Suzuki, Yuichiro Justin
author_facet Suzuki, Yuichiro Justin
author_sort Suzuki, Yuichiro Justin
collection PubMed
description The current belief is that amino acid sequences in protein structures are defined by DNA sequences. I challenge this concept by hypothesizing that an arginine (Arg) residue in the protein structure can post-translationally be converted to a proline (Pro) residue through a redox mechanism. Reactive oxygen species promote the formation of protein carbonylation, particularly on Arg and Pro residues, which both produce glutamyl semialdehyde. Our previous studies suggested that the Pro-to-glutamyl semialdehyde reaction could be reversible in the biological system, thereby opening up a pathway for the conversion of Arg to glutamyl semialdehyde by oxidation, and subsequently, to Pro by reduction in the protein structure. Our mass spectrometry and immunoblotting experiments provided evidence of the occurrence of the Arg-to-Pro conversion at position 108 (R108P) of the peroxiredoxin 6 (Prx6) protein in biological tissues and cells. In the human brain, Prx6 (R108P) occurs, and some Alzheimer’s brains exhibit increased Prx6 (R108P) levels, while others show decreased levels, indicating the complexity of redox processes in the disease state. I propose that Prx6 (R108P), as well as other post-translationally regulated protein Arg-to-Pro conversions, occur in the human body and play physiological and pathological roles.
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spelling pubmed-93184052022-07-27 Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains Suzuki, Yuichiro Justin Life (Basel) Hypothesis The current belief is that amino acid sequences in protein structures are defined by DNA sequences. I challenge this concept by hypothesizing that an arginine (Arg) residue in the protein structure can post-translationally be converted to a proline (Pro) residue through a redox mechanism. Reactive oxygen species promote the formation of protein carbonylation, particularly on Arg and Pro residues, which both produce glutamyl semialdehyde. Our previous studies suggested that the Pro-to-glutamyl semialdehyde reaction could be reversible in the biological system, thereby opening up a pathway for the conversion of Arg to glutamyl semialdehyde by oxidation, and subsequently, to Pro by reduction in the protein structure. Our mass spectrometry and immunoblotting experiments provided evidence of the occurrence of the Arg-to-Pro conversion at position 108 (R108P) of the peroxiredoxin 6 (Prx6) protein in biological tissues and cells. In the human brain, Prx6 (R108P) occurs, and some Alzheimer’s brains exhibit increased Prx6 (R108P) levels, while others show decreased levels, indicating the complexity of redox processes in the disease state. I propose that Prx6 (R108P), as well as other post-translationally regulated protein Arg-to-Pro conversions, occur in the human body and play physiological and pathological roles. MDPI 2022-06-28 /pmc/articles/PMC9318405/ /pubmed/35888057 http://dx.doi.org/10.3390/life12070967 Text en © 2022 by the author. 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 Hypothesis
Suzuki, Yuichiro Justin
Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains
title Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains
title_full Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains
title_fullStr Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains
title_full_unstemmed Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains
title_short Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer’s Brains
title_sort post-translationally regulated protein arginine-to-proline conversion in alzheimer’s brains
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318405/
https://www.ncbi.nlm.nih.gov/pubmed/35888057
http://dx.doi.org/10.3390/life12070967
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