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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 03 2023
Historique:
received: 19 06 2022
accepted: 03 03 2023
medline: 29 3 2023
entrez: 27 3 2023
pubmed: 28 3 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36973249
doi: 10.1038/s41467-023-37215-3
pii: 10.1038/s41467-023-37215-3
pmc: PMC10042849
doi:

Substances chimiques

Glycoside Hydrolases EC 3.2.1.-
Immunoglobulin G 0
Polysaccharides 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1705

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : R01AI149297
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
ID : R01GM096973

Informations de copyright

© 2023. The Author(s).

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Auteurs

Beatriz Trastoy (B)

Structural Glycobiology Laboratory, Biocruces Health Research Institute, Barakaldo, Bizkaia, 48903, Spain. beatriz.trastoy@gmail.com.
Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain. beatriz.trastoy@gmail.com.
Ikerbasque, Basque Foundation for Science, 48009, Bilbao, Spain. beatriz.trastoy@gmail.com.

Jonathan J Du (JJ)

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Javier O Cifuente (JO)

Structural Glycobiology Laboratory, Biocruces Health Research Institute, Barakaldo, Bizkaia, 48903, Spain.
Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.

Lorena Rudolph (L)

University of Lübeck, Center of Structural and Cell Biology in Medicine (CSCM), Institute of Chemistry and Metabolomics, Ratzeburger Allee 160, 23562, Lübeck, Germany.

Mikel García-Alija (M)

Structural Glycobiology Laboratory, Biocruces Health Research Institute, Barakaldo, Bizkaia, 48903, Spain.
Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.

Erik H Klontz (EH)

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Daniel Deredge (D)

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, 21201, USA.

Nazneen Sultana (N)

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Chau G Huynh (CG)

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Maria W Flowers (MW)

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Chao Li (C)

Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.

Diego E Sastre (DE)

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Lai-Xi Wang (LX)

Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, 20742, USA.

Francisco Corzana (F)

Departamento Química and Centro de Investigación en Síntesis Quı́mica, Universidad de La Rioja, 26006, Rioja, Spain.

Alvaro Mallagaray (A)

University of Lübeck, Center of Structural and Cell Biology in Medicine (CSCM), Institute of Chemistry and Metabolomics, Ratzeburger Allee 160, 23562, Lübeck, Germany. alvaro.mallagaraydebenito@uni-luebeck.de.

Eric J Sundberg (EJ)

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, 30322, USA. eric.sundberg@emory.edu.

Marcelo E Guerin (ME)

Structural Glycobiology Laboratory, Biocruces Health Research Institute, Barakaldo, Bizkaia, 48903, Spain. mrcguerin@gmail.com.
Structural Glycobiology Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain. mrcguerin@gmail.com.
Ikerbasque, Basque Foundation for Science, 48009, Bilbao, Spain. mrcguerin@gmail.com.

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