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PreprintCited by 14Glycosylation and Glycoproteins ResearchBiochemical and Structural CharacterizationBacterial Genetics and Biotechnology

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Glycosylation of serine/threonine-rich intrinsically disordered regions of membrane-associated proteins in streptococci

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Rahman, Mohammad M., Zamakhaeva, Svetlana, Rush, Jeffrey S., Chaton, Catherine T., Kenner, Cameron W., Hla, Yin Mon, Tsui, Ho-Ching Tiffany, Uversky, Vladimir N., Winkler, Malcolm E., Korotkov, Konstantin V., Korotkova, Natalia·2024·Nature Communications
DOI 10.1101/2024.05.05.592596PMC PMC12041528

Preprint — published as 10.1038/s41467-025-58692-8

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Abstract

Proteins harboring intrinsically disordered regions (IDRs) lacking stable secondary or tertiary structures are abundant across the three domains of life. These regions have not been systematically studied in prokaryotes. Our genome-wide analysis identifies extracytoplasmic serine/threonine-rich IDRs in several biologically important membrane-associated proteins in streptococci. We demonstrate that these IDRs are glycosylated with glucose by glycosyltransferases GtrB and PgtC2 in Streptococcus pyogenes and Streptococcus pneumoniae , and with N-acetylgalactosamine by a Pgf-dependent mechanism in Streptococcus mutans . The absence of glycosylation leads to a defect in biofilm formation under ethanol-stressed conditions in S. mutans . We link this phenotype to the C-terminal IDR of the post-translocation chaperone PrsA. Our data reveal that O -linked glycosylation protects the IDR-containing proteins from proteolytic degradation and is critical for the biological function of PrsA in biofilm formation.

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Metadata

Authors
Rahman, M. M., Zamakhaeva, S., Rush, J. S., Chaton, C. T., Kenner, C. W., Hla, Y. M., Tsui, H.-C. T., Uversky, V. N., Winkler, M. E., Korotkov, K. V., & Korotkova, N.
Affiliations
  • University of Kentucky (US)
  • Indiana University Bloomington (US)
  • University of South Florida (US)
Corresponding author
Korotkova, Natalia
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2024-05-05
Volume
16
Issue
1
Pages
4011-4011
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2024.05.05.592596
PMC
PMC12041528
OpenAlex
W4409923212
Cited by
14
References
1
Citations by year
2026: 8 · 2025: 5 · 2024: 1
FWCI
3.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • UKnowledge (University of Kentucky) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Hypothesis Fund
  • U.S. Department of Health and Human Services (R35GM131767, R01DE028916)
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R21AI149366)
  • National Taiwan University
  • National Institutes of Health (5r21ai146945-02)
  • National Institute of General Medical Sciences (R35GM131767)
  • National Institute of Allergy and Infectious Diseases (R21AI149366)
  • National Institute of Dental and Craniofacial Research (R01DE028916)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
intrinsically disordered regions, O-glycosylation, membrane-associated proteins, Streptococcus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans, N-acetylgalactosamine, PrsA, biofilm formation, ethanol stress, proteolysis

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