RT Journal Article
SR Electronic
T1 Extensive substrate recognition by the streptococcal antibody-degrading enzymes IdeS and EndoS
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.19.496714
DO 10.1101/2022.06.19.496714
A1 Abigail S L Sudol
A1 John Butler
A1 Dylan P Ivory
A1 Ivo Tews
A1 Max Crispin
YR 2022
UL http://biorxiv.org/content/early/2022/06/19/2022.06.19.496714.abstract
AB The cleavage of human IgG antibodies is a potent immune evasion mechanism utilised by some pathogenic bacteria. The Streptococcus pyogenes bacterium, which has the capacity to cause necrotising fasciitis, employs multiple enzymes to deactivate the human adaptive immune system. Two such proteins, IdeS and EndoS, prevent immune detection by ablating the immune effector functions of IgG, by cleavage and deglycosylation of its Fc region, respectively. Their fine specificity for IgG has led to a wide range of clinical and biotechnology applications, with IdeS having received clinical approval facilitating organ transplantation in hypersensitised individuals, while EndoS has found application in engineering antibody glycosylation. Here, we present crystal structures of IdeS and EndoS in complex with their IgG1 Fc substrate, with both enzymes exhibiting exquisite target specificity. The IdeS protease is shown encasing the antibody hinge target, but also recognises the Fc globular domains. In contrast, the glycan hydrolase domain in EndoS traps the Fc glycan in a flipped-out conformation, while additional antibody specificity is driven by protein recognition by the so-called carbohydrate binding module. Understanding the molecular basis of antibody recognition by bacterial enzymes will facilitate the development of next-generation enzymes.Competing Interest StatementThe authors have declared no competing interest.