Molecular recognition of Escherichia coli R1-type core lipooligosaccharide by DC-SIGN
Ferran Nieto-Fabregat,
Angela Marseglia,
Michel Thépaut,
Jean-Philippe Kleman,
Massilia Abbas,
Aline Le Roy,
Christine Ebel,
Meriem Maalej,
Jean-Pierre Simorre,
Cedric Laguri,
Antonio Molinaro,
Alba Silipo,
Franck Fieschi,
Roberta Marchetti
Affiliations
Ferran Nieto-Fabregat
Department of Chemical Science, University of Naples Federico II Via Cinthia 4, 80126 Naples, Italy
Angela Marseglia
Department of Chemical Science, University of Naples Federico II Via Cinthia 4, 80126 Naples, Italy
Michel Thépaut
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Jean-Philippe Kleman
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Massilia Abbas
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Aline Le Roy
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Christine Ebel
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Meriem Maalej
Department of Chemical Science, University of Naples Federico II Via Cinthia 4, 80126 Naples, Italy; University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Jean-Pierre Simorre
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Cedric Laguri
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France
Antonio Molinaro
Department of Chemical Science, University of Naples Federico II Via Cinthia 4, 80126 Naples, Italy
Alba Silipo
Department of Chemical Science, University of Naples Federico II Via Cinthia 4, 80126 Naples, Italy
Franck Fieschi
University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, 41 Avenue des Martyrs, 38000 Grenoble, France; Institut Universitaire de France (IUF), Paris, France
Roberta Marchetti
Department of Chemical Science, University of Naples Federico II Via Cinthia 4, 80126 Naples, Italy; Corresponding author
Summary: Due to their ability to recognize carbohydrate structures, lectins emerged as potential receptors for bacterial lipopolysaccharides (LPS). Despite growing interest in investigating the association between host receptor lectins and exogenous glycan ligands, the molecular mechanisms underlying bacterial recognition by human lectins are still not fully understood. We contributed to fill this gap by unveiling the molecular basis of the interaction between the lipooligosaccharide of Escherichia coli and the dendritic cell-specific intracellular adhesion molecules (ICAM)-3 grabbing non-integrin (DC-SIGN). Specifically, a combination of different techniques, including fluorescence microscopy, surface plasmon resonance, NMR spectroscopy, and computational studies, demonstrated that DC-SIGN binds to the purified deacylated R1 lipooligosaccharide mainly through the recognition of its outer core pentasaccharide, which acts as a crosslinker between two different tetrameric units of DC-SIGN. Our results contribute to a better understanding of DC-SIGN-LPS interaction and may support the development of pharmacological and immunostimulatory strategies for bacterial infections, prevention, and therapy.
