Peptidoglycan Modifications Tune the Stability and Function of the Innate Immune Receptor Nod2.
| Autor: | Melnyk JE; †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States., Mohanan V; †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States., Schaefer AK; †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States., Hou CW; †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States., Grimes CL; †Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of the American Chemical Society [J Am Chem Soc] 2015 Jun 10; Vol. 137 (22), pp. 6987-90. Date of Electronic Publication: 2015 Jun 02. |
| DOI: | 10.1021/jacs.5b01607 |
| Abstrakt: | Natural modifications of peptidoglycan modulate the innate immune response. Peptidoglycan derivatives activate this response via the intracellular innate immune receptor, Nod2. To probe how these modifications alter the response, a novel and efficient carbohydrate synthesis was developed to allow for late-stage modification of the amine at the 2-position. Modification of the carbohydrate was found to be important for stabilizing Nod2 and generating the proper response. The native Nod2 ligands demonstrate a significant increase in the cellular stability of Nod2. Moreover, changing the identity of the natural ligands at the carbohydrate 2-position allows for the Nod2-dependent immune response to be either up-regulated or down-regulated. The ligand structure can be adjusted to tune the Nod2 response, suggesting that other innate immune receptors and their ligands could use a similar strategy. |
| Databáze: | MEDLINE |
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