| Structural highlights
Function
ENDOS_STRP1 Endoglucosidase that acts as a host immune evasion factor by mediating hydrolysis of the N-linked glycan from the Fc region of host immunoglobulin-gamma (IgG) during infection (PubMed:11406581, PubMed:11598100, PubMed:12438337, PubMed:18182097, PubMed:20357243, PubMed:21619648, PubMed:22551167, PubMed:22747414, PubMed:24668806, PubMed:24753590, PubMed:29760474, PubMed:30102520, PubMed:31092533). Specifically catalyzes the hydrolysis of the beta-1,4 linkage between the first two N-acetylglucosamine residues of the complex-type N-linked glycan located on 'Asn-297' of the Fc region of IgG antibodies (IGHG1, IGHG2, IGHG3 or IGHG4), thereby preventing interaction between IgGs and Fc receptors and ability to activate the complement pathway (PubMed:11406581, PubMed:11598100, PubMed:12438337, PubMed:20357243, PubMed:21619648, PubMed:31092533). Shows a specificity for biantennary complex type N-glycans; does neither cleave larger complex type glycans nor oligomannose and nor hybrid-type glycans (PubMed:22551167, PubMed:26156869). Specifically acts on IgGs; does not act on immunoglobulin alpha, beta, delta or mu (PubMed:11598100).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
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-beta-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.
Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases.,Trastoy B, Du JJ, Cifuente JO, Rudolph L, Garcia-Alija M, Klontz EH, Deredge D, Sultana N, Huynh CG, Flowers MW, Li C, Sastre DE, Wang LX, Corzana F, Mallagaray A, Sundberg EJ, Guerin ME Nat Commun. 2023 Mar 27;14(1):1705. doi: 10.1038/s41467-023-37215-3. PMID:36973249[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Collin M, Olsén A. EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG. EMBO J. 2001 Jun 15;20(12):3046-55. PMID:11406581 doi:10.1093/emboj/20.12.3046
- ↑ Collin M, Olsén A. Effect of SpeB and EndoS from Streptococcus pyogenes on human immunoglobulins. Infect Immun. 2001 Nov;69(11):7187-9. PMID:11598100 doi:10.1128/IAI.69.11.7187-7189.2001
- ↑ Collin M, Svensson MD, Sjöholm AG, Jensenius JC, Sjöbring U, Olsén A. EndoS and SpeB from Streptococcus pyogenes inhibit immunoglobulin-mediated opsonophagocytosis. Infect Immun. 2002 Dec;70(12):6646-51. PMID:12438337 doi:10.1128/IAI.70.12.6646-6651.2002
- ↑ Allhorn M, Olsén A, Collin M. EndoS from Streptococcus pyogenes is hydrolyzed by the cysteine proteinase SpeB and requires glutamic acid 235 and tryptophans for IgG glycan-hydrolyzing activity. BMC Microbiol. 2008 Jan 8;8:3. PMID:18182097 doi:10.1186/1471-2180-8-3
- ↑ Allhorn M, Briceño JG, Baudino L, Lood C, Olsson ML, Izui S, Collin M. The IgG-specific endoglycosidase EndoS inhibits both cellular and complement-mediated autoimmune hemolysis. Blood. 2010 Jun 17;115(24):5080-8. PMID:20357243 doi:10.1182/blood-2009-08-239020
- ↑ Sjögren J, Okumura CY, Collin M, Nizet V, Hollands A. Study of the IgG endoglycosidase EndoS in group A streptococcal phagocyte resistance and virulence. BMC Microbiol. 2011 May 27;11:120. PMID:21619648 doi:10.1186/1471-2180-11-120
- ↑ Goodfellow JJ, Baruah K, Yamamoto K, Bonomelli C, Krishna B, Harvey DJ, Crispin M, Scanlan CN, Davis BG. An endoglycosidase with alternative glycan specificity allows broadened glycoprotein remodelling. J Am Chem Soc. 2012 May 16;134(19):8030-3. PMID:22551167 doi:10.1021/ja301334b
- ↑ Huang W, Giddens J, Fan SQ, Toonstra C, Wang LX. Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions. J Am Chem Soc. 2012 Jul 25;134(29):12308-18. PMID:22747414 doi:10.1021/ja3051266
- ↑ Dixon EV, Claridge JK, Harvey DJ, Baruah K, Yu X, Vesiljevic S, Mattick S, Pritchard LK, Krishna B, Scanlan CN, Schnell JR, Higgins MK, Zitzmann N, Crispin M. Fragments of bacterial endoglycosidase s and immunoglobulin g reveal subdomains of each that contribute to deglycosylation. J Biol Chem. 2014 May 16;289(20):13876-89. PMID:24668806 doi:10.1074/jbc.M113.532812
- ↑ Trastoy B, Lomino JV, Pierce BG, Carter LG, Gunther S, Giddens JP, Snyder GA, Weiss TM, Weng Z, Wang LX, Sundberg EJ. Crystal structure of Streptococcus pyogenes EndoS, an immunomodulatory endoglycosidase specific for human IgG antibodies. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6714-9. doi:, 10.1073/pnas.1322908111. Epub 2014 Apr 21. PMID:24753590 doi:http://dx.doi.org/10.1073/pnas.1322908111
- ↑ Sjögren J, Cosgrave EF, Allhorn M, Nordgren M, Björk S, Olsson F, Fredriksson S, Collin M. EndoS and EndoS2 hydrolyze Fc-glycans on therapeutic antibodies with different glycoform selectivity and can be used for rapid quantification of high-mannose glycans. Glycobiology. 2015 Oct;25(10):1053-63. PMID:26156869 doi:10.1093/glycob/cwv047
- ↑ Trastoy B, Klontz E, Orwenyo J, Marina A, Wang LX, Sundberg EJ, Guerin ME. Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S. Nat Commun. 2018 May 14;9(1):1874. doi: 10.1038/s41467-018-04300-x. PMID:29760474 doi:http://dx.doi.org/10.1038/s41467-018-04300-x
- ↑ Tong X, Li T, Li C, Wang LX. Generation and Comparative Kinetic Analysis of New Glycosynthase Mutants from Streptococcus pyogenes Endoglycosidases for Antibody Glycoengineering. Biochemistry. 2018 Sep 4;57(35):5239-5246. PMID:30102520 doi:10.1021/acs.biochem.8b00719
- ↑ Naegeli A, Bratanis E, Karlsson C, Shannon O, Kalluru R, Linder A, Malmström J, Collin M. Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis. J Exp Med. 2019 Jul 1;216(7):1615-1629. PMID:31092533 doi:10.1084/jem.20190293
- ↑ Trastoy B, Du JJ, Cifuente JO, Rudolph L, García-Alija M, Klontz EH, Deredge D, Sultana N, Huynh CG, Flowers MW, Li C, Sastre DE, Wang LX, Corzana F, Mallagaray A, Sundberg EJ, Guerin ME. Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases. Nat Commun. 2023 Mar 27;14(1):1705. PMID:36973249 doi:10.1038/s41467-023-37215-3
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