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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9318405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT suzukiyuichirojustin posttranslationallyregulatedproteinargininetoprolineconversioninalzheimersbrains |