{"abstract":[{"lang":"eng","text":"<jats:title>Abstract</jats:title><jats:p>The C-type lectin receptor langerin plays a vital role in the mammalian defense against invading pathogens. Its function hinges on the affinity to its co-factor Ca<jats:sup>2+</jats:sup> which in turn is regulated by the pH. We studied the structural consequences of pro-tonating the allosteric pH-sensor histidine H294 by molecular dynamics simulations (total simulation time: about 120 μs) and Markov models. We discovered a mechanism in which the signal that the pH has dropped is transferred to the Ca<jats:sup>2+</jats:sup>-binding site without transferring the initial proton. Instead, protonation of H294 unlocks a conformation in which a protonated lysine side-chain forms a hydrogen bond with a Ca<jats:sup>2+</jats:sup>-coordinating aspartic acid. This destabilizes Ca<jats:sup>2+</jats:sup> in the binding pocket, which we probed by steered molecular dynamics. After Ca<jats:sup>2+</jats:sup>-release, the proton is likely transferred to the aspartic acid and stabilized by a dyad with a nearby glutamic acid, triggering a conformational transition and thus preventing Ca<jats:sup>2+</jats:sup>-rebinding.</jats:p>"}],"publication":"bioRxiv","publication_status":"published","citation":{"mla":"Joswig, Jan-O., et al. “Molecular Mechanism of the PH-Dependent Calcium Affinity in Langerin.” <i>BioRxiv</i>, 2020.","apa":"Joswig, J.-O., Anders, J., Zhang, H., Rademacher, C., &#38; Keller, B. G. (2020). Molecular Mechanism of the pH-Dependent Calcium Affinity in Langerin. <i>BioRxiv</i>.","short":"J.-O. Joswig, J. Anders, H. Zhang, C. Rademacher, B.G. Keller, BioRxiv (2020).","bibtex":"@article{Joswig_Anders_Zhang_Rademacher_Keller_2020, title={Molecular Mechanism of the pH-Dependent Calcium Affinity in Langerin}, journal={bioRxiv}, author={Joswig, Jan-O. and Anders, Jennifer and Zhang, Hengxi and Rademacher, Christoph and Keller, Bettina G.}, year={2020} }","ama":"Joswig J-O, Anders J, Zhang H, Rademacher C, Keller BG. Molecular Mechanism of the pH-Dependent Calcium Affinity in Langerin. <i>bioRxiv</i>. 2020.","chicago":"Joswig, Jan-O., Jennifer Anders, Hengxi Zhang, Christoph Rademacher, and Bettina G. Keller. “Molecular Mechanism of the PH-Dependent Calcium Affinity in Langerin.” <i>BioRxiv</i>, 2020.","ieee":"J.-O. Joswig, J. Anders, H. Zhang, C. Rademacher, and B. G. Keller, “Molecular Mechanism of the pH-Dependent Calcium Affinity in Langerin,” <i>bioRxiv</i>. 2020."},"status":"public","title":"Molecular Mechanism of the pH-Dependent Calcium Affinity in Langerin","keyword":["pc2-ressources"],"author":[{"full_name":"Joswig, Jan-O.","last_name":"Joswig","first_name":"Jan-O."},{"first_name":"Jennifer","last_name":"Anders","full_name":"Anders, Jennifer"},{"first_name":"Hengxi","full_name":"Zhang, Hengxi","last_name":"Zhang"},{"last_name":"Rademacher","full_name":"Rademacher, Christoph","first_name":"Christoph"},{"first_name":"Bettina G.","full_name":"Keller, Bettina G.","last_name":"Keller"}],"user_id":"61189","_id":"16953","date_created":"2020-05-15T07:08:54Z","language":[{"iso":"eng"}],"project":[{"name":"Computing Resources Provided by the Paderborn Center for Parallel Computing","_id":"52"}],"date_updated":"2022-01-06T06:53:00Z","type":"preprint","year":"2020"}