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Revealing the human mucinome

Stacy A. Malaker (), Nicholas M. Riley, D. Judy Shon, Kayvon Pedram, Venkatesh Krishnan, Oliver Dorigo and Carolyn R. Bertozzi ()
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Stacy A. Malaker: Stanford University
Nicholas M. Riley: Stanford University
D. Judy Shon: Stanford University
Kayvon Pedram: Stanford University
Venkatesh Krishnan: Stanford University
Oliver Dorigo: Stanford University
Carolyn R. Bertozzi: Stanford University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31062-4

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