{"entity": "researcher", "timestamp": "2026-08-15T06:57:21.738Z", "family": "Nilges", "given": "Michael", "initials": "M", "orcid": "0000-0002-1451-8092", "affiliations": ["Structural Bioinformatics Unit, Department of Structural Biology and Chemistry, C3BI, Institut Pasteur, CNRS UMR3528, Paris, France."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/ebfd5336137d4eaabde8f4f9baed470a.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/ebfd5336137d4eaabde8f4f9baed470a"}}, "publications": [{"entity": "publication", "iuid": "b2a30a6011bb47659582e0b4cdce2803", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b2a30a6011bb47659582e0b4cdce2803.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b2a30a6011bb47659582e0b4cdce2803"}}, "title": "The hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies.", "authors": [{"family": "Izadi", "given": "Arman", "initials": "A", "orcid": "0000-0002-0262-1017", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d6f1927cfc643818a0a3a1b8602af14.json"}}, {"family": "Karami", "given": "Yasaman", "initials": "Y", "orcid": "0000-0001-8413-2665", "researcher": {"href": "https://publications.scilifelab.se/researcher/a71f08b3f3794e66b7adae400c14f142.json"}}, {"family": "Bratanis", "given": "Eleni", "initials": "E", "orcid": "0000-0002-0636-6658", "researcher": {"href": "https://publications.scilifelab.se/researcher/c935953f81fc4d8eb6a9b9ddb7774c1b.json"}}, {"family": "Wrighton", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-3378-7925", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b5821cc01364325a4b9fe177e7f6e33.json"}}, {"family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}}, {"family": "Nyblom", "given": "Maria", "initials": "M"}, {"family": "Olofsson", "given": "Berit", "initials": "B", "orcid": "0009-0009-0602-2183", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ad483473b044b7dbc7e6c61ef1c0a73.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Tang", "given": "Di", "initials": "D", "orcid": "0000-0001-6323-9375", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2a27467c4094d9f8d8f8402efa333f4.json"}}, {"family": "Sundwall", "given": "Martin", "initials": "M", "orcid": "0000-0002-0114-6613", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0080c10aa64cd7b073813c8ebc0bc7.json"}}, {"family": "Godzwon", "given": "Magdalena", "initials": "M"}, {"family": "Chao", "given": "Yashuan", "initials": "Y", "orcid": "0000-0002-0295-3142", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed7bd7c821754977ba516c3e1c04eceb.json"}}, {"family": "Toledo", "given": "Alejandro Gomez", "initials": "AG", "orcid": "0000-0002-2103-7158", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e9d9a5e2dc148c9bcdc07f2b4a17ebc.json"}}, {"family": "Schmidt", "given": "Tobias", "initials": "T", "orcid": "0000-0001-9943-4121", "researcher": {"href": "https://publications.scilifelab.se/researcher/2eba2593dde24540a7d70aa3b593e4fc.json"}}, {"family": "Ohlin", "given": "Mats", "initials": "M", "orcid": "0000-0002-5105-1938", "researcher": {"href": "https://publications.scilifelab.se/researcher/fda1d1ed0b074a04a69b0c8b036dd001.json"}}, {"family": "Nilges", "given": "Michael", "initials": "M", "orcid": "0000-0002-1451-8092", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebfd5336137d4eaabde8f4f9baed470a.json"}}, {"family": "Malmstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0002-2889-7169", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad3c999da10c41e4a3afda2718815083.json"}}, {"family": "Bahnan", "given": "Wael", "initials": "W"}, {"family": "Shannon", "given": "Oonagh", "initials": "O", "orcid": "0000-0001-8291-8189", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed4685bab7584028a070fc5a829bd386.json"}}, {"family": "Malmstr\u00f6m", "given": "Lars", "initials": "L", "orcid": "0000-0001-9885-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e99f34fb854beb8d810b05fe941057.json"}}, {"family": "Nordenfelt", "given": "Pontus", "initials": "P", "orcid": "0000-0002-9481-9951", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa3418ab23a4ec48c037d6d6ddea5b5.json"}}], "type": "journal article", "published": "2024-04-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "3600", "issn-l": "2041-1723"}, "abstract": "Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25. Despite having reduced binding, the IgG3 version promotes stronger phagocytosis of bacteria. Using atomic simulations, we show that IgG3's Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions with immune cells. We replaced the hinge of IgG1 with four different IgG3-hinge segment subclasses, IgGhxx. Hinge-engineering does not diminish binding as with IgG3 but enhances opsonic function, where a 47 amino acid hinge is comparable to IgG3 in function. IgGh47 shows improved protection against S. pyogenes in a systemic infection mouse model, suggesting that IgGh47 has promise as a preclinical therapeutic candidate. Importantly, the enhanced opsonic function of IgGh47 is generalizable to diverse S. pyogenes strains from clinical isolates. We generated IgGh47 versions of anti-SARS-CoV-2 mAbs to broaden the biological applicability, and these also exhibit strongly enhanced opsonic function compared to the IgG1 subclass. The improved function of the IgGh47 subclass in two distant biological systems provides new insights into antibody function.", "doi": "10.1038/s41467-024-47928-8", "pmid": "38678029", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11055898"}, {"db": "pii", "key": "10.1038/s41467-024-47928-8"}], "notes": [], "created": "2024-11-08T09:49:22.468Z", "modified": "2025-10-17T13:05:07.370Z"}, {"entity": "publication", "iuid": "03a9bb0f8fa14a829220610e1ac822c4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/03a9bb0f8fa14a829220610e1ac822c4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/03a9bb0f8fa14a829220610e1ac822c4"}}, "title": "Structural determination of Streptococcus pyogenes M1 protein interactions with human immunoglobulin G using integrative structural biology.", "authors": [{"family": "Khakzad", "given": "Hamed", "initials": "H", "orcid": "0000-0002-8556-0650", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b030c1452c4dc9b430deffdf493e6f.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Karami", "given": "Yasaman", "initials": "Y", "orcid": "0000-0001-8413-2665", "researcher": {"href": "https://publications.scilifelab.se/researcher/a71f08b3f3794e66b7adae400c14f142.json"}}, {"family": "Chowdhury", "given": "Sounak", "initials": "S"}, {"family": "Bergdahl", "given": "Gizem Ert\u00fcrk", "initials": "GE", "orcid": "0000-0001-9719-6609", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3671f82049b4e8e96fd45b0e0351642.json"}}, {"family": "Nilges", "given": "Michael", "initials": "M", "orcid": "0000-0002-1451-8092", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebfd5336137d4eaabde8f4f9baed470a.json"}}, {"family": "Tran Van Nhieu", "given": "Guy", "initials": "G"}, {"family": "Malmstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0002-2889-7169", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad3c999da10c41e4a3afda2718815083.json"}}, {"family": "Malmstr\u00f6m", "given": "Lars", "initials": "L", "orcid": "0000-0001-9885-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e99f34fb854beb8d810b05fe941057.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "PLoS Comput. Biol.", "issn": "1553-7358", "volume": "17", "issue": "1", "pages": "e1008169", "issn-l": "1553-734X"}, "abstract": "Streptococcus pyogenes (Group A streptococcus; GAS) is an important human pathogen responsible for mild to severe, life-threatening infections. GAS expresses a wide range of virulence factors, including the M family proteins. The M proteins allow the bacteria to evade parts of the human immune defenses by triggering the formation of a dense coat of plasma proteins surrounding the bacteria, including IgGs. However, the molecular level details of the M1-IgG interaction have remained unclear. Here, we characterized the structure and dynamics of this interaction interface in human plasma on the surface of live bacteria using integrative structural biology, combining cross-linking mass spectrometry and molecular dynamics (MD) simulations. We show that the primary interaction is formed between the S-domain of M1 and the conserved IgG Fc-domain. In addition, we show evidence for a so far uncharacterized interaction between the A-domain and the IgG Fc-domain. Both these interactions mimic the protein G-IgG interface of group C and G streptococcus. These findings underline a conserved scavenging mechanism used by GAS surface proteins that block the IgG-receptor (Fc\u03b3R) to inhibit phagocytic killing. We additionally show that we can capture Fab-bound IgGs in a complex background and identify XLs between the constant region of the Fab-domain and certain regions of the M1 protein engaged in the Fab-mediated binding. Our results elucidate the M1-IgG interaction network involved in inhibition of phagocytosis and reveal important M1 peptides that can be further investigated as future vaccine targets.", "doi": "10.1371/journal.pcbi.1008169", "pmid": "33411763", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PCOMPBIOL-D-20-01263"}, {"db": "pmc", "key": "PMC7817036"}], "notes": [], "created": "2021-12-03T12:29:48.339Z", "modified": "2021-12-03T12:29:48.505Z"}]}