Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases

Beatriz Trastoy (), Jonathan J. Du, Javier O. Cifuente, Lorena Rudolph, Mikel García-Alija, Erik H. Klontz, Daniel Deredge, Nazneen Sultana, Chau G. Huynh, Maria W. Flowers, Chao Li, Diego E. Sastre, Lai-Xi Wang, Francisco Corzana, Alvaro Mallagaray (), Eric J. Sundberg () and Marcelo E. Guerin ()
Additional contact information
Beatriz Trastoy: Biocruces Health Research Institute
Jonathan J. Du: Emory University School of Medicine
Javier O. Cifuente: Biocruces Health Research Institute
Lorena Rudolph: Institute of Chemistry and Metabolomics
Mikel García-Alija: Biocruces Health Research Institute
Erik H. Klontz: University of Maryland School of Medicine
Daniel Deredge: University of Maryland School of Pharmacy
Nazneen Sultana: Emory University School of Medicine
Chau G. Huynh: Emory University School of Medicine
Maria W. Flowers: Emory University School of Medicine
Chao Li: University of Maryland
Diego E. Sastre: Emory University School of Medicine
Lai-Xi Wang: University of Maryland
Francisco Corzana: Universidad de La Rioja
Alvaro Mallagaray: Institute of Chemistry and Metabolomics
Eric J. Sundberg: Emory University School of Medicine
Marcelo E. Guerin: Biocruces Health Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Streptococcus pyogenes serotypes secrete two multi-modular endo-β-N-acetylglucosaminidases, EndoS and EndoS2, that specifically deglycosylate the conserved N-glycan at Asn297 on IgG Fc, disabling antibody-mediated effector functions. Amongst thousands of known carbohydrate-active enzymes, EndoS and EndoS2 represent just a handful of enzymes that are specific to the protein portion of the glycoprotein substrate, not just the glycan component. Here, we present the cryoEM structure of EndoS in complex with the IgG1 Fc fragment. In combination with small-angle X-ray scattering, alanine scanning mutagenesis, hydrolytic activity measurements, enzyme kinetics, nuclear magnetic resonance and molecular dynamics analyses, we establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by EndoS and EndoS2. Our results provide a rational basis from which to engineer novel enzymes with antibody and glycan selectivity for clinical and biotechnological applications.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37215-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37215-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37215-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().