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Calcium‐Independent Activation of an Allosteric Network in Langerin by Heparin Oligosaccharides
Author(s) -
Hanske Jonas,
Wawrzinek Robert,
Geissner Andreas,
Wamhoff EikeChristian,
Sellrie Katrin,
Schmidt Henrik,
Seeberger Peter H.,
Rademacher Christoph
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700027
Subject(s) - langerin , birbeck granules , glycan , allosteric regulation , glycobiology , chemistry , biochemistry , lectin , biophysics , microbiology and biotechnology , receptor , biology , glycoprotein , immunology , antigen , dendritic cell , langerhans cell
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 Ca 2+ ‐dependent binding site, heparins have been proposed to make additional contacts to a secondary, Ca 2+ ‐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 Ca 2+ and activated a previously identified intradomain allosteric network of Langerin (thus far only associated with Ca 2+ affinity and release). We propose a communication hub between these two binding sites, which sheds new light on modulatory functions of Langerin–heparin interactions.