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

Author

Listed:
  • Mohammad M. Rahman

    (University of Kentucky)

  • Svetlana Zamakhaeva

    (University of Kentucky)

  • Jeffrey S. Rush

    (University of Kentucky)

  • Catherine T. Chaton

    (University of Kentucky)

  • Cameron W. Kenner

    (University of Kentucky)

  • Yin Mon Hla

    (Indiana University Bloomington)

  • Ho-Ching Tiffany Tsui

    (Indiana University Bloomington)

  • Vladimir N. Uversky

    (University of South Florida)

  • Malcolm E. Winkler

    (Indiana University Bloomington)

  • Konstantin V. Korotkov

    (University of Kentucky)

  • Natalia Korotkova

    (University of Kentucky
    University of Kentucky)

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. 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.

Suggested Citation

  • 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. Ko, 2025. "Glycosylation of serine/threonine-rich intrinsically disordered regions of membrane-associated proteins in streptococci," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58692-8
    DOI: 10.1038/s41467-025-58692-8
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    1. Robert M. Cleverley & Zoe J. Rutter & Jeanine Rismondo & Federico Corona & Ho-Ching Tiffany Tsui & Fuad A. Alatawi & Richard A. Daniel & Sven Halbedel & Orietta Massidda & Malcolm E. Winkler & Richard, 2019. "The cell cycle regulator GpsB functions as cytosolic adaptor for multiple cell wall enzymes," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    2. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    3. Keren Lasker & Steven Boeynaems & Vinson Lam & Daniel Scholl & Emma Stainton & Adam Briner & Maarten Jacquemyn & Dirk Daelemans & Ashok Deniz & Elizabeth Villa & Alex S. Holehouse & Aaron D. Gitler & , 2022. "The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Jeffrey S. Rush & Svetlana Zamakhaeva & Nicholas R. Murner & Pan Deng & Andrew J. Morris & Cameron W. Kenner & Ian Black & Christian Heiss & Parastoo Azadi & Konstantin V. Korotkov & Göran Widmalm & N, 2025. "Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    5. David J. Busch & Justin R. Houser & Carl C. Hayden & Michael B. Sherman & Eileen M. Lafer & Jeanne C. Stachowiak, 2015. "Intrinsically disordered proteins drive membrane curvature," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    6. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    7. Jeffrey S. Rush & Prakash Parajuli & Alessandro Ruda & Jian Li & Amol Arunrao Pohane & Svetlana Zamakhaeva & Mohammad M. Rahman & Jennifer C. Chang & Artemis Gogos & Cameron W. Kenner & Gérard Lambeau, 2022. "PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Nicholas C. Tang & Jonathan C. Su & Yulia Shmidov & Garrett Kelly & Sonal Deshpande & Parul Sirohi & Nikhil Peterson & Ashutosh Chilkoti, 2024. "Synthetic intrinsically disordered protein fusion tags that enhance protein solubility," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Chiara Ardiccioni & Oliver B. Clarke & David Tomasek & Habon A. Issa & Desiree C. von Alpen & Heather L. Pond & Surajit Banerjee & Kanagalaghatta R. Rajashankar & Qun Liu & Ziqiang Guan & Chijun Li & , 2016. "Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    10. Sylvie Manuse & Nicolas L. Jean & Mégane Guinot & Jean-Pierre Lavergne & Cédric Laguri & Catherine M. Bougault & Michael S. VanNieuwenhze & Christophe Grangeasse & Jean-Pierre Simorre, 2016. "Structure–function analysis of the extracellular domain of the pneumococcal cell division site positioning protein MapZ," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    11. Aurore Fleurie & Christian Lesterlin & Sylvie Manuse & Chao Zhao & Caroline Cluzel & Jean-Pierre Lavergne & Mirita Franz-Wachtel & Boris Macek & Christophe Combet & Erkin Kuru & Michael S. VanNieuwenh, 2014. "MapZ marks the division sites and positions FtsZ rings in Streptococcus pneumoniae," Nature, Nature, vol. 516(7530), pages 259-262, December.
    12. H. Wang & X. Yan & H. Aigner & A. Bracher & N. D. Nguyen & W. Y. Hee & B. M. Long & G. D. Price & F. U. Hartl & M. Hayer-Hartl, 2019. "Rubisco condensate formation by CcmM in β-carboxysome biogenesis," Nature, Nature, vol. 566(7742), pages 131-135, February.
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