Glycosylation of serine/threonine-rich intrinsically disordered regions of membrane-associated proteins in streptococci
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. Here, 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.
Authors
- Ho‐Ching Tiffany Tsui (ORCID: https://orcid.org/0000-0003-0849-874X)
- Malcolm E. Winkler (ORCID: https://orcid.org/0000-0002-1482-2588)
- Cameron W. Kenner
- Jeffrey S. Rush (ORCID: https://orcid.org/0000-0002-3674-8008)
- Konstantin V. Korotkov (ORCID: https://orcid.org/0000-0002-2182-6843)
- Svetlana Zamakhaeva (ORCID: https://orcid.org/0000-0001-9971-4211)
- Natalia Korotkova (ORCID: https://orcid.org/0000-0002-8696-4892)
- Catherine T. Chaton (ORCID: https://orcid.org/0000-0002-2843-3559)
- Vladimir Nikolaevich Uversky (ORCID: https://orcid.org/0000-0002-4037-5857)
- Yin Mon Hla (ORCID: https://orcid.org/0009-0009-1076-4622)
- Mohammad M. Rahman (ORCID: https://orcid.org/0000-0003-2881-5132)
Institutions
- University of Kentucky HealthCare (US)
- University of Kentucky (US)
- University of South Florida (US)
- Indiana University Bloomington (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-29
- DOI
- https://doi.org/10.1038/s41467-025-58692-8
- Citations
- 6
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 4.84
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Taiwan University
- National Institute of General Medical Sciences
- National Institute of Dental and Craniofacial Research