Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli
Abstract Lymphostatin is a key virulence factor of enteropathogenic and enterohaemorrhagic Escherichia coli, playing roles in bacterial colonisation of the gut and in the inhibition of lymphocyte proliferation and proinflammatory responses. The protein’s glycosyltransferase and cysteine protease mot...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60995-9 |
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| author | Matthias Griessmann Tim Rasmussen Vanessa J. Flegler Christian Kraft Ronja Schneider Max Hateley Lukas Spantzel Mark P. Stevens Michael Börsch Bettina Böttcher |
| author_facet | Matthias Griessmann Tim Rasmussen Vanessa J. Flegler Christian Kraft Ronja Schneider Max Hateley Lukas Spantzel Mark P. Stevens Michael Börsch Bettina Böttcher |
| author_sort | Matthias Griessmann |
| collection | DOAJ |
| description | Abstract Lymphostatin is a key virulence factor of enteropathogenic and enterohaemorrhagic Escherichia coli, playing roles in bacterial colonisation of the gut and in the inhibition of lymphocyte proliferation and proinflammatory responses. The protein’s glycosyltransferase and cysteine protease motifs are required for activity against lymphocytes, but high-resolution structural information has proven elusive. Here, we describe the structure of lymphostatin from enteropathogenic E. coli O127:H6, determined by electron cryo-microscopy at different pH values. We observe three conformations of a highly complex molecule with two glycosyltransferase domains, one PaToxP-like protease domain, an ADP-ribosyltransferase domain, a vertex domain and a delivery domain. Long linkers hold these domains together and occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains. Lymphostatin binds to bovine T-lymphocytes and HEK-293T cells, forming clusters at the plasma membrane that are internalized. With six distinct domains, lymphostatin can be regarded as a multitool of pathogenic Escherichia coli, enabling complex interactions with host cells. |
| format | Article |
| id | doaj-art-bd0ac145035a41d181643e79bdb82aec |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bd0ac145035a41d181643e79bdb82aec2025-08-20T03:27:18ZengNature PortfolioNature Communications2041-17232025-06-0116111410.1038/s41467-025-60995-9Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coliMatthias Griessmann0Tim Rasmussen1Vanessa J. Flegler2Christian Kraft3Ronja Schneider4Max Hateley5Lukas Spantzel6Mark P. Stevens7Michael Börsch8Bettina Böttcher9University of Würzburg, Rudolf Virchow Center and BiocenterUniversity of Würzburg, Rudolf Virchow Center and BiocenterUniversity of Würzburg, Rudolf Virchow Center and BiocenterUniversity of Würzburg, Rudolf Virchow Center and BiocenterUniversity of Würzburg, Rudolf Virchow Center and BiocenterUniversity of Edinburgh, The Roslin Institute and Royal (Dick) School of Veterinary StudiesJena University Hospital, Single Molecule Microscopy GroupUniversity of Edinburgh, The Roslin Institute and Royal (Dick) School of Veterinary StudiesJena University Hospital, Single Molecule Microscopy GroupUniversity of Würzburg, Rudolf Virchow Center and BiocenterAbstract Lymphostatin is a key virulence factor of enteropathogenic and enterohaemorrhagic Escherichia coli, playing roles in bacterial colonisation of the gut and in the inhibition of lymphocyte proliferation and proinflammatory responses. The protein’s glycosyltransferase and cysteine protease motifs are required for activity against lymphocytes, but high-resolution structural information has proven elusive. Here, we describe the structure of lymphostatin from enteropathogenic E. coli O127:H6, determined by electron cryo-microscopy at different pH values. We observe three conformations of a highly complex molecule with two glycosyltransferase domains, one PaToxP-like protease domain, an ADP-ribosyltransferase domain, a vertex domain and a delivery domain. Long linkers hold these domains together and occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains. Lymphostatin binds to bovine T-lymphocytes and HEK-293T cells, forming clusters at the plasma membrane that are internalized. With six distinct domains, lymphostatin can be regarded as a multitool of pathogenic Escherichia coli, enabling complex interactions with host cells.https://doi.org/10.1038/s41467-025-60995-9 |
| spellingShingle | Matthias Griessmann Tim Rasmussen Vanessa J. Flegler Christian Kraft Ronja Schneider Max Hateley Lukas Spantzel Mark P. Stevens Michael Börsch Bettina Böttcher Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli Nature Communications |
| title | Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli |
| title_full | Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli |
| title_fullStr | Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli |
| title_full_unstemmed | Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli |
| title_short | Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli |
| title_sort | structure of lymphostatin a large multi functional virulence factor of pathogenic escherichia coli |
| url | https://doi.org/10.1038/s41467-025-60995-9 |
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