title: Calcium-Independent Activation of an Allosteric Network in Langerin by Heparin Oligosaccharides.
abstract: The C-type lectin receptor Langerin is a glycan-binding protein that serves as an uptake receptor on Langerhans cells and is essential for the formation of Birbeck granules. Whereas most Langerin ligands are recognized by a canonical Ca2+-dependent binding site, heparins have been proposed to make additional contacts to a secondary, Ca2+-independent site. Glycan array screening and biomolecular NMR spectroscopy were employed to investigate the molecular mechanism of these interactions. We observed that binding of heparin hexasaccharides to a secondary site did not require the presence of Ca2+and activated a previously identified intradomain allosteric network of Langerin (thus far only associated with Ca2+affinity and release). We propose a communication hub between these two binding sites, which sheds new light on modulatory functions of Langerin-heparin interactions.
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.
authors.forename: Jonas
authors.identifier: 0000-0002-8854-3012
authors.initials: J
authors.lastname: Hanske
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.
authors.forename: Robert
authors.identifier: 0000-0002-1186-7625
authors.initials: R
authors.lastname: Wawrzinek
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.|Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geissner
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.|Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Eike-Christian
authors.identifier: 0000-0002-8665-5512
authors.initials: EC
authors.lastname: Wamhoff
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Sellrie
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.|Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Peter H
authors.identifier: 0000-0003-3394-8466
authors.initials: PH
authors.lastname: Seeberger
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany.|Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Christoph
authors.identifier: 0000-0001-7082-7239
authors.initials: C
authors.lastname: Rademacher
mesh_terms: D000494:Allosteric Regulation; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D008024:Ligands; D037241:Mannose-Binding Lectins; D009844:Oligosaccharides; D011994:Recombinant Proteins; D006493:Heparin; D002118:Calcium
keywords: Birbeck granules; Langerin; allosterism; glycan-binding proteins; heparin; molecular recognition