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Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics
Chondroitin sulfate proteoglycans (CSPGs) control key events in human health and disease and are composed of chondroitin sulfate (CS) polysaccharide(s) attached to different core proteins. Detailed information on the biological effects of site-specific CS structures is scarce as the polysaccharides...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424144/ https://www.ncbi.nlm.nih.gov/pubmed/37453717 http://dx.doi.org/10.1016/j.mcpro.2023.100617 |
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author | Noborn, Fredrik Nilsson, Jonas Sihlbom, Carina Nikpour, Mahnaz Kjellén, Lena Larson, Göran |
author_facet | Noborn, Fredrik Nilsson, Jonas Sihlbom, Carina Nikpour, Mahnaz Kjellén, Lena Larson, Göran |
author_sort | Noborn, Fredrik |
collection | PubMed |
description | Chondroitin sulfate proteoglycans (CSPGs) control key events in human health and disease and are composed of chondroitin sulfate (CS) polysaccharide(s) attached to different core proteins. Detailed information on the biological effects of site-specific CS structures is scarce as the polysaccharides are typically released from their core proteins prior to analysis. Here we present a novel glycoproteomic approach for site-specific sequencing of CS modifications from human urine. Software-assisted and manual analysis revealed that certain core proteins carried CS with abundant sulfate modifications, while others carried CS with lower levels of sulfation. Inspection of the amino acid sequences surrounding the attachment sites indicated that the acidity of the attachment site motifs increased the levels of CS sulfation, and statistical analysis confirmed this relationship. However, not only the acidity but also the sequence and characteristics of specific amino acids in the proximity of the serine glycosylation site correlated with the degree of sulfation. These results demonstrate attachment site-specific characteristics of CS polysaccharides of CSPGs in human urine and indicate that this novel method may assist in elucidating the biosynthesis and functional roles of CSPGs in cellular physiology. |
format | Online Article Text |
id | pubmed-10424144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-104241442023-08-15 Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics Noborn, Fredrik Nilsson, Jonas Sihlbom, Carina Nikpour, Mahnaz Kjellén, Lena Larson, Göran Mol Cell Proteomics Research Chondroitin sulfate proteoglycans (CSPGs) control key events in human health and disease and are composed of chondroitin sulfate (CS) polysaccharide(s) attached to different core proteins. Detailed information on the biological effects of site-specific CS structures is scarce as the polysaccharides are typically released from their core proteins prior to analysis. Here we present a novel glycoproteomic approach for site-specific sequencing of CS modifications from human urine. Software-assisted and manual analysis revealed that certain core proteins carried CS with abundant sulfate modifications, while others carried CS with lower levels of sulfation. Inspection of the amino acid sequences surrounding the attachment sites indicated that the acidity of the attachment site motifs increased the levels of CS sulfation, and statistical analysis confirmed this relationship. However, not only the acidity but also the sequence and characteristics of specific amino acids in the proximity of the serine glycosylation site correlated with the degree of sulfation. These results demonstrate attachment site-specific characteristics of CS polysaccharides of CSPGs in human urine and indicate that this novel method may assist in elucidating the biosynthesis and functional roles of CSPGs in cellular physiology. American Society for Biochemistry and Molecular Biology 2023-07-14 /pmc/articles/PMC10424144/ /pubmed/37453717 http://dx.doi.org/10.1016/j.mcpro.2023.100617 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Noborn, Fredrik Nilsson, Jonas Sihlbom, Carina Nikpour, Mahnaz Kjellén, Lena Larson, Göran Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics |
title | Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics |
title_full | Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics |
title_fullStr | Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics |
title_full_unstemmed | Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics |
title_short | Mapping the Human Chondroitin Sulfate Glycoproteome Reveals an Unexpected Correlation Between Glycan Sulfation and Attachment Site Characteristics |
title_sort | mapping the human chondroitin sulfate glycoproteome reveals an unexpected correlation between glycan sulfation and attachment site characteristics |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10424144/ https://www.ncbi.nlm.nih.gov/pubmed/37453717 http://dx.doi.org/10.1016/j.mcpro.2023.100617 |
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