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Revealing the human mucinome

Mucin domains are densely O-glycosylated modular protein domains found in various extracellular and transmembrane proteins. Mucin-domain glycoproteins play important roles in many human diseases, such as cancer and cystic fibrosis, but the scope of the mucinome remains poorly defined. Recently, we c...

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Autores principales: Malaker, Stacy A., Riley, Nicholas M., Shon, D. Judy, Pedram, Kayvon, Krishnan, Venkatesh, Dorigo, Oliver, Bertozzi, Carolyn R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209528/
https://www.ncbi.nlm.nih.gov/pubmed/35725833
http://dx.doi.org/10.1038/s41467-022-31062-4
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author Malaker, Stacy A.
Riley, Nicholas M.
Shon, D. Judy
Pedram, Kayvon
Krishnan, Venkatesh
Dorigo, Oliver
Bertozzi, Carolyn R.
author_facet Malaker, Stacy A.
Riley, Nicholas M.
Shon, D. Judy
Pedram, Kayvon
Krishnan, Venkatesh
Dorigo, Oliver
Bertozzi, Carolyn R.
author_sort Malaker, Stacy A.
collection PubMed
description Mucin domains are densely O-glycosylated modular protein domains found in various extracellular and transmembrane proteins. Mucin-domain glycoproteins play important roles in many human diseases, such as cancer and cystic fibrosis, but the scope of the mucinome remains poorly defined. Recently, we characterized a bacterial O-glycoprotease, StcE, and demonstrated that an inactive point mutant retains binding selectivity for mucin-domain glycoproteins. In this work, we leverage inactive StcE to selectively enrich and identify mucin-domain glycoproteins from complex samples like cell lysate and crude ovarian cancer patient ascites fluid. Our enrichment strategy is further aided by an algorithm to assign confidence to mucin-domain glycoprotein identifications. This mucinomics platform facilitates detection of hundreds of glycopeptides from mucin domains and highly overlapping populations of mucin-domain glycoproteins from ovarian cancer patients. Ultimately, we demonstrate our mucinomics approach can reveal key molecular signatures of cancer from in vitro and ex vivo sources.
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spelling pubmed-92095282022-06-22 Revealing the human mucinome Malaker, Stacy A. Riley, Nicholas M. Shon, D. Judy Pedram, Kayvon Krishnan, Venkatesh Dorigo, Oliver Bertozzi, Carolyn R. Nat Commun Article Mucin domains are densely O-glycosylated modular protein domains found in various extracellular and transmembrane proteins. Mucin-domain glycoproteins play important roles in many human diseases, such as cancer and cystic fibrosis, but the scope of the mucinome remains poorly defined. Recently, we characterized a bacterial O-glycoprotease, StcE, and demonstrated that an inactive point mutant retains binding selectivity for mucin-domain glycoproteins. In this work, we leverage inactive StcE to selectively enrich and identify mucin-domain glycoproteins from complex samples like cell lysate and crude ovarian cancer patient ascites fluid. Our enrichment strategy is further aided by an algorithm to assign confidence to mucin-domain glycoprotein identifications. This mucinomics platform facilitates detection of hundreds of glycopeptides from mucin domains and highly overlapping populations of mucin-domain glycoproteins from ovarian cancer patients. Ultimately, we demonstrate our mucinomics approach can reveal key molecular signatures of cancer from in vitro and ex vivo sources. Nature Publishing Group UK 2022-06-20 /pmc/articles/PMC9209528/ /pubmed/35725833 http://dx.doi.org/10.1038/s41467-022-31062-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Malaker, Stacy A.
Riley, Nicholas M.
Shon, D. Judy
Pedram, Kayvon
Krishnan, Venkatesh
Dorigo, Oliver
Bertozzi, Carolyn R.
Revealing the human mucinome
title Revealing the human mucinome
title_full Revealing the human mucinome
title_fullStr Revealing the human mucinome
title_full_unstemmed Revealing the human mucinome
title_short Revealing the human mucinome
title_sort revealing the human mucinome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209528/
https://www.ncbi.nlm.nih.gov/pubmed/35725833
http://dx.doi.org/10.1038/s41467-022-31062-4
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