Intradomain Allosteric Network Modulates Calcium Affinity of the C-Type Lectin Receptor Langerin.
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,...
| Publicado en: | Journal of the American Chemical Society Vol. 139; no. 37; pp. 12176 - 12187 |
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| Autores principales: | , , , , , , , , |
| Formato: | Artículo |
| Publicado: |
American Chemical Society
9/21/2017
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| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=125212635&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 125212635 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 9/21/2017 vid: 139 iid: 37 pid: 997 pub: American Chemical Society artinfo: ui: 125212635 10.1021/jacs.6b05458 ppf: 12176 ppct: 11 formats: tig: atl: Intradomain Allosteric Network Modulates Calcium Affinity of the C-Type Lectin Receptor Langerin. aug: au: Hanske, Jonas Shanina, Elena Rademacher, Christoph Aleksic, Stevan Keller, Bettina G. Ballaschk, Martin Beerbaum, Monika Schmieder, Peter Jurk, Marcel affil: 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 Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Straße 10, 13125 Berlin, Germany Department of Bioinformatics, Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany su: Antigens Immune response Pattern perception Pathogenic microorganisms Diagnostic microbiology Glycan structure sug: subj: Antigens Immune response Pattern perception Pathogenic microorganisms Diagnostic microbiology Glycan structure ab: 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 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 affinity depending on the pH, thereby promoting fast ligand release. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2017 holdings: @attributes: islocal: N |
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