| First Author | Sastre DE | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 24 | Pages | 6994-7007.e12 |
| PubMed ID | 39437779 | Mgi Jnum | J:390627 |
| Mgi Id | MGI:7779264 | Doi | 10.1016/j.cell.2024.09.038 |
| Citation | Sastre DE, et al. (2024) Potent efficacy of an IgG-specific endoglycosidase against IgG-mediated pathologies. Cell |
| abstractText | Endo-beta-N-acetylglucosaminidases (ENGases) that specifically hydrolyze the Asn297-linked glycan on immunoglobulin G (IgG) antibodies, the major molecular determinant of fragment crystallizable (Fc) gamma receptor (FcgammaR) binding, are exceedingly rare. All previously characterized IgG-specific ENGases are multi-domain proteins secreted as an immune evasion strategy by Streptococcus pyogenes strains. Here, using in silico analysis and mass spectrometry techniques, we identified a family of single-domain ENGases secreted by pathogenic corynebacterial species that exhibit strict specificity for IgG antibodies. By X-ray crystallographic and surface plasmon resonance analyses, we found that the most catalytically efficient IgG-specific ENGase family member recognizes both protein and glycan components of IgG. Employing in vivo models, we demonstrated the remarkable efficacy of this IgG-specific ENGase in mitigating numerous pathologies that rely on FcgammaR-mediated effector functions, including T and B lymphocyte depletion, autoimmune hemolytic anemia, and antibody-dependent enhancement of dengue disease, revealing its potential for treating and/or preventing a wide range of IgG-mediated diseases in humans. |
