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TitleMechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1705, Year 2023
Publish dateMar 27, 2023
AuthorsBeatriz 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 / Marcelo E Guerin /
PubMed AbstractBacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Streptococcus pyogenes serotypes secrete two multi- ...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.
External linksNat Commun / PubMed:36973249 / PubMed Central
MethodsEM (single particle)
Resolution4.6 Å
Structure data

EMDB-15205: cryoEM structure of the catalytically inactive EndoS from S. pyogenes in complex with the Fc region of immunoglobulin G1
PDB-8a64: cryoEM structure of the catalytically inactive EndoS from S. pyogenes in complex with the Fc region of immunoglobulin G1.
Method: EM (single particle) / Resolution: 4.6 Å

Source
  • streptococcus pyogenes (bacteria)
  • homo sapiens (human)
KeywordsHYDROLASE / Endoglycosidase S / EndoS / endo-b-N-acetylglucosaminidase / Fc region / antibody / immunoglobulin G1 / Streptococcus pyogenes / N-glycans

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