8a64
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==cryoEM structure of the catalytically inactive EndoS from S. pyogenes in complex with the Fc region of immunoglobulin G1.== | |
| + | <StructureSection load='8a64' size='340' side='right'caption='[[8a64]], [[Resolution|resolution]] 4.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8a64]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A64 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A64 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8a64 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a64 OCA], [https://pdbe.org/8a64 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a64 RCSB], [https://www.ebi.ac.uk/pdbsum/8a64 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a64 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ENDOS_STRP1 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).<ref>PMID:11406581</ref> <ref>PMID:11598100</ref> <ref>PMID:12438337</ref> <ref>PMID:18182097</ref> <ref>PMID:20357243</ref> <ref>PMID:21619648</ref> <ref>PMID:22551167</ref> <ref>PMID:22747414</ref> <ref>PMID:24668806</ref> <ref>PMID:24753590</ref> <ref>PMID:26156869</ref> <ref>PMID:29760474</ref> <ref>PMID:30102520</ref> <ref>PMID:31092533</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:36973249</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8a64" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Streptococcus pyogenes]] | ||
| + | [[Category: Cifuente JO]] | ||
| + | [[Category: Du JJ]] | ||
| + | [[Category: Guerin ME]] | ||
| + | [[Category: Sundberg EJ]] | ||
| + | [[Category: Trastoy B]] | ||
Current revision
cryoEM structure of the catalytically inactive EndoS from S. pyogenes in complex with the Fc region of immunoglobulin G1.
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