Bacterial Polysaccharide Specificity of the Pattern Recognition Receptor Langerin Is Highly Species-dependent*

  1. Christoph Rademacher‡,§1
  1. From the ‡Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam 14424, Germany,
  2. the §Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin, Berlin 14195, Germany,
  3. the Department of Cell and Molecular Biology, Department of Immunology and Microbial Science and Department of Chemical Physiology, Scripps Research Institute, La Jolla, California 92037,
  4. the ‖N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia, and
  5. the **Robert Koch Institute, Wernigerode Branch, National Reference Centre for Salmonellae and other Bacterial Enteric Pathogens, Wernigerode 38855, Germany
  1. ↵1 To whom correspondence should be addressed: Dept. of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Wissenschaftspark Golm, Am Mühlenberg 1, 14424 Potsdam, Germany. Tel.: 49-331-567-9358; E-mail: Christoph.Rademacher{at}mpikg.mpg.de.

  1. Edited by Luke O'Neill

Abstract

The recognition of pathogen surface polysaccharides by glycan-binding proteins is a cornerstone of innate host defense. Many members of the C-type lectin receptor family serve as pattern recognition receptors facilitating pathogen uptake, antigen processing, and immunomodulation. Despite the high evolutionary pressure in host-pathogen interactions, it is still widely assumed that genetic homology conveys similar specificities. Here, we investigate the ligand specificities of the human and murine forms of the myeloid C-type lectin receptor langerin for simple and complex ligands augmented by structural insight into murine langerin. Although the two homologs share the same three-dimensional structure and recognize simple ligands identically, a screening of more than 300 bacterial polysaccharides revealed highly diverging avidity and selectivity for larger and more complex glycans. Structural and evolutionary conservation analysis identified a highly variable surface adjacent to the canonic binding site, potentially forming a secondary site of interaction for large glycans.

Footnotes

  • ↵* This work was supported by Deutsche Forschungsgemeinschaft Grant 1944/2–1 (to C. R.) and Consortium for Functional Glycomics Grant U54GM62116 (to J. C. P.). The authors declare that they have no conflicts of interest with the contents of this article.

  • ↵Graphic This article contains supplemental Table S1 and Figs. S1–S4.

  • The atomic coordinates and structure factors (codes 5K8Y and 5M62) have been deposited in the Protein Data Bank (http://wwpdb.org/).

  • Received August 4, 2016.
  • Revision received November 29, 2016.
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  1. First Published on November 30, 2016 doi: 10.1074/jbc.M116.751750 The Journal of Biological Chemistry 292, 862-871.
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