Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors
van Sorge, Nina M.; Bonsor, Daniel A.; Deng, Liwen; Lindahl, Erik; Schmitt, Verena; Lyndin, Mykola; Schmidt, Alexej; Nilsson, Olof R.; Brizuela, Jaime; Boero, Elena; Sundberg, Eric J.; van Strijp, Jos A.G.; Doran, Kelly S.; Singer, Bernhard B.; Lindahl, Gunnar; McCarthy, Alex J.
(2021) EMBO Journal, volume 40, issue 7, pp. 1 - 20
(Article)
Abstract
Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host
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binding partner characterised. We report here that surface-expressed β protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.
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Keywords: Adhesin, IgI, immunoglobulin superfamily, receptor, Streptococcus agalactiae, Streptococcus agalactiae/metabolism, Cricetinae, Cricetulus, Humans, Adhesins, Bacterial/chemistry, GPI-Linked Proteins/chemistry, Animals, Cell Adhesion Molecules/chemistry, Antigens, CD/chemistry, Protein Binding, Carcinoembryonic Antigen/chemistry, HeLa Cells, Binding Sites, CHO Cells, General Biochemistry,Genetics and Molecular Biology, General Immunology and Microbiology, Molecular Biology, General Neuroscience, Research Support, Non-U.S. Gov't, Journal Article, Research Support, N.I.H., Extramural
ISSN: 0261-4189
Publisher: Nature Publishing Group
Note: Funding Information: The authors thank Carla J.C. de Haas, Piet Aerts, Kok P.M. van Kessel (UMC Utrecht, Utrecht, The Netherlands), Birgit Maranca‐Hüwel, Bärbel Gobs‐Hevelke (University of Duisburg‐Essen, Germany) and Margaretha Stålhammar‐Carlemalm (Lund University, Sweden) for excellent technical support and invaluable help. We thank Paul Sullam (University of California, USA) for providing strains. We also wish to thank the support staff of Beamlines of 12‐2 and ID23‐D at the Stanford Synchrotron Radiation Lightsource and the Advanced Photon Source for their aid in data collection, respectively. We thank Irene M. Mavridis (Institute of Child Health, Greece) and José R. Penadés (Imperial College London, UK) for critical reading of the manuscript. This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement 700862 (to A.J.M, J.A.G), Deutsche Forschungsgemeinschaft DFG grant SI‐1558/3‐1 (to B.B.S.), The Swedish Research Council grant K2011‐56X‐09490‐21‐6(to G.L), The Foundation Olle Engkvist Byggmästare (to G.L.) and the National Institutes of Health R01 NS116716 (to K.S.D.) S. sanguinis Funding Information: The authors thank Carla J.C. de Haas, Piet Aerts, Kok P.M. van Kessel (UMC Utrecht, Utrecht, The Netherlands), Birgit Maranca-H?wel, B?rbel Gobs-Hevelke (University of Duisburg-Essen, Germany) and Margaretha St?lhammar-Carlemalm (Lund University, Sweden) for excellent technical support and invaluable help. We thank Paul Sullam (University of California, USA) for providing S. sanguinis strains. We also wish to thank the support staff of Beamlines of 12-2 and ID23-D at the Stanford Synchrotron Radiation Lightsource and the Advanced Photon Source for their aid in data collection, respectively. We thank Irene M. Mavridis (Institute of Child Health, Greece) and Jos? R. Penad?s (Imperial College London, UK) for critical reading of the manuscript. This work was supported by the European Union?s Horizon 2020 Research and Innovation Programme under Grant Agreement 700862 (to A.J.M, J.A.G), Deutsche Forschungsgemeinschaft DFG grant SI-1558/3-1 (to B.B.S.), The Swedish Research Council grant K2011-56X-09490-21-6(to G.L), The Foundation Olle Engkvist Byggm?stare (to G.L.) and the National Institutes of Health R01 NS116716 (to K.S.D.) Publisher Copyright: © 2021 The Authors. Published under the terms of the CC BY 4.0 license © 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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