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Extensive substrate recognition by the streptococcal antibody-degrading enzymes IdeS and EndoS

DOI: 10.1038/s41467-022-35340-z DOI Help

Authors: Abigail S. L. Sudol (University of Southampton) , John Butler (University of Southampton) , Dylan P. Ivory (University of Southampton) , Ivo Tews (University of Southampton) , Max Crispin (University of Southampton)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 13

State: Published (Approved)
Published: December 2022
Diamond Proposal Number(s): 29835

Open Access Open Access

Abstract: Enzymatic cleavage of IgG antibodies is a common strategy used by pathogenic bacteria to ablate immune effector function. The Streptococcus pyogenes bacterium secretes the protease IdeS and the glycosidase EndoS, which specifically catalyse cleavage and deglycosylation of human IgG, respectively. IdeS has received clinical approval for kidney transplantation in hypersensitised individuals, while EndoS has found application in engineering antibody glycosylation. We present crystal structures of both enzymes in complex with their IgG1 Fc substrate, which was achieved using Fc engineering to disfavour preferential Fc crystallisation. The IdeS protease displays extensive Fc recognition and encases the antibody hinge. Conversely, the glycan hydrolase domain in EndoS traps the Fc glycan in a “flipped-out” conformation, while additional recognition of the Fc peptide is driven by the so-called carbohydrate binding module. In this work, we reveal the molecular basis of antibody recognition by bacterial enzymes, providing a template for the development of next-generation enzymes.

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Other Facilities: ID30A-3 at ESRF

Added On: 23/12/2022 09:00


Discipline Tags:

Pathogens Infectious Diseases Biotechnology Health & Wellbeing Structural biology Engineering & Technology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)