Work

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

Year: 2025

Type: article

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.

Source: Nature Communications

DOI: 10.1038/s41467-025-58692-8

Authors: Mohammad M. Rahman, Svetlana Zamakhaeva, Jeffrey S. Rush, Catherine T. Chaton, Cameron W. Kenner, Yin Mon Hla, Ho-Ching Tiffany Tsui, Vladimir N. Uversky, Malcolm E. Winkler, Konstantin V. Korotkov, Natalia Korotkova

Institutions: University of Kentucky, Indiana University Bloomington, Indiana University, University of South Florida

Language: English

Topic: Glycosylation and Glycoproteins Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: Hypothesis Fund, U.S. Department of Health and Human Services, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Taiwan University, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research

Awards: Biosynthesis, structure and function of cell wall in Streptococcus mutans, G1162158422, G1518161034, Mechanisms of resistance against the human group IIA secreted phospholipase A2 in Group B Streptococcus, G3807772842, New Regulatory Interactions and Circuits that Mediate the Dynamics, Homeostasis, and Stress Responses of Peptidoglycan Synthesis in the Superbug Streptococcus pneumoniae, Identification of the factors contributing to resistance of Group A Streptococcus to human group IIA secreted phospholipase A2, G7051240393

OpenAlex ID: W4409923212

FWCI: 3.275

Cites: 120

Cited by: 14

Related to: 10