Intradomain Allosteric Network Modulates Calcium Affinity of the C‑Type Lectin Receptor Langerin

Jonas Hanske, Stevan Aleksić, Martin Ballaschk, Marcel Jurk, Elena Shanina, Monika Beerbaum, Peter Schmieder, Bettina G. Keller, and Christoph Rademacher – 2016

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 Ca2+ 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 Ca2+ affinity depending on the pH, thereby promoting fast ligand release.

Titel
Intradomain Allosteric Network Modulates Calcium Affinity of the C‑Type Lectin Receptor Langerin
Verfasser
Jonas Hanske, Stevan Aleksić, Martin Ballaschk, Marcel Jurk, Elena Shanina, Monika Beerbaum, Peter Schmieder, Bettina G. Keller, and Christoph Rademacher
Datum
2016
Kennung
10.1021/acs.jctc.5b00498
Zitierweise
J. Am. Chem. Soc., 2016, 138 (37), 12176–12186
Art
Text
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