title: Intradomain Allosteric Network Modulates Calcium Affinity of the C-Type Lectin Receptor Langerin.
abstract: Antigen uptake and processing by innate immune cells is crucial to initiate the immune response. Therein, the endocytic C-type lectin receptors serve as pattern recognition receptors, detecting pathogens by their glycan structures. Herein, we studied the carbohydrate recognition domain of Langerin, a C-type lectin receptor involved in the host defense against viruses such as HIV and influenza as well as bacteria and fungi. Using a combination of nuclear magnetic resonance and molecular dynamics simulations, we unraveled the molecular determinants underlying cargo capture and release encoded in the receptor architecture. Our findings revealed receptor dynamics over several time scales associated with binding and release of the essential cofactor Ca(2+) controlled by the coupled motions of two loops. Applying mutual information theory and site-directed mutagenesis, we identified an allosteric intradomain network that modulates the Ca(2+) affinity depending on the pH, thereby promoting fast ligand release.
authors: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces , Am Mühlenberg 1, 14424 Potsdam, Germany.|Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors: Jonas
authors: J
authors: Hanske
authors: Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors: Stevan
authors: S
authors: Aleksić
authors: Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.|Leibniz-Institut für Molekulare Pharmakologie , Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors: Martin
authors: M
authors: Ballaschk
authors: Department of Bioinformatics, Max Planck Institute for Molecular Genetics , Ihnestraße 63-73, 14195 Berlin, Germany.
authors: Marcel
authors: M
authors: Jurk
authors: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces , Am Mühlenberg 1, 14424 Potsdam, Germany.|Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors: Elena
authors: E
authors: Shanina
authors: Leibniz-Institut für Molekulare Pharmakologie , Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors: Monika
authors: M
authors: Beerbaum
authors: Leibniz-Institut für Molekulare Pharmakologie , Robert-Rössle-Straße 10, 13125 Berlin, Germany.
authors: Peter
authors: P
authors: Schmieder
authors: Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors: Bettina G
authors: BG
authors: Keller
authors: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces , Am Mühlenberg 1, 14424 Potsdam, Germany.|Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin , Takustraße 3, 14195 Berlin, Germany.
authors: Christoph
authors: C
authors: Rademacher
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type / Q000737:chemistry*; D037241:Mannose-Binding Lectins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D002118:Calcium