@article{eba28afd84254dafa4c4354cfc1e3c9e,
title = "Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors",
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 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.",
keywords = "Adhesin, IgI, Streptococcus agalactiae, immunoglobulin superfamily, receptor",
author = "{van Sorge}, {Nina M.} and Bonsor, {Daniel A.} and Liwen Deng and Erik Lindahl and Verena Schmitt and Mykola Lyndin and Alexej Schmidt and Nilsson, {Olof R.} and Jaime Brizuela and Elena Boero and Sundberg, {Eric J.} and {van Strijp}, {Jos A. G.} and Doran, {Kelly S.} and Singer, {Bernhard B.} and Gunnar Lindahl and McCarthy, {Alex J.}",
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‐H{\"u}wel, B{\"a}rbel Gobs‐Hevelke (University of Duisburg‐Essen, Germany) and Margaretha St{\aa}lhammar‐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 Jos{\'e} R. Penad{\'e}s (Imperial College London, UK) for critical reading of the manuscript. This work was supported by the European Union{\textquoteright}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{\"a}stare (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: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY 4.0 license Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = apr,
day = "1",
doi = "https://doi.org/10.15252/embj.2020106103",
language = "English",
volume = "40",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "7",
}