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

DOI: 10.1038/s41467-023-37215-3

Authors: Beatriz Trastoy (Biocruces Health Research Institute; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); Ikerbasque, Basque Foundation for Science) , Jonathan J. Du (Emory University School of Medicine) , Javier O. Cifuente (Biocruces Health Research Institute; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Lorena Rudolph (University of Lübeck) , Mikel Garcia-Alija (Biocruces Health Research Institute; Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Erik H. Klontz (University of Maryland School of Medicine) , Daniel Deredge (University of Maryland School of Medicine) , 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 (University of Lübeck) , Eric J. Sundberg (Emory University School of Medicine) , Marcelo E. Guerin (Biocruces Health Research Institute; Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA); Ikerbasque, Basque Foundation for Science)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 14

State: Published (Approved)
Published: March 2023
Diamond Proposal Number(s): 1534 , 28360

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.

Journal Keywords: Bacterial immune evasion; Glycobiology; Hydrolases; Structural biology

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS

Added On: 31/03/2023 11:28

Documents:
s41467-023-37215-3.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)