Selective Boosting of CCR7-Acting Chemokines; Short Peptides Boost Chemokines with Short Basic Tails, Longer Peptides Boost Chemokines with Long Basic Tails
| Autor: | Emma Probst Brandum, Astrid Sissel Jørgensen, Marina Barrio Calvo, Katja Spiess, Francis C. Peterson, Zhang Yang, Brian F. Volkman, Christopher T. Veldkamp, Mette Marie Rosenkilde, Christoffer Knak Goth, Gertrud Malene Hjortø |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Receptors
CCR7 endocrine system QH301-705.5 T-Lymphocytes Ligands Catalysis Inorganic Chemistry basic peptide Basic peptide CCL19 Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy biased signaling Chemokine CCL21 Organic Chemistry CCR7 CCL21 General Medicine Computer Science Applications Chemistry Biased signaling Chemokine CCL19 Peptides Signal Transduction |
| Zdroj: | Brandum, E P, Jørgensen, A S, Calvo, M B, Spiess, K, Peterson, F C, Yang, Z, Volkman, B F, Veldkamp, C T, Rosenkilde, M M, Goth, C K & Hjortø, G M 2022, ' Selective Boosting of CCR7-Acting Chemokines; Short Peptides Boost Chemokines with Short Basic Tails, Longer Peptides Boost Chemokines with Long Basic Tails ', International Journal of Molecular Sciences, vol. 23, no. 3, 1397 . https://doi.org/10.3390/ijms23031397 International Journal of Molecular Sciences, Vol 23, Iss 1397, p 1397 (2022) International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1397 |
| DOI: | 10.3390/ijms23031397 |
| Popis: | The chemokine receptor CCR7 and its ligands CCL19 and CCL21 regulate the lymph node homing of dendritic cells and naïve T-cells and the following induction of a motile DC-T cell priming state. Although CCL19 and CCL21 bind CCR7 with similar affinities, CCL21 is a weak agonist compared to CCL19. Using a chimeric chemokine, CCL19CCL21N-term|C-term, harboring the N-terminus and the C-terminus of CCL21 attached to the core domain of CCL19, we show that these parts of CCL21 act in a synergistic manner to lower ligand potency and determine the way CCL21 engages with CCR7. We have published that a naturally occurring basic C-terminal fragment of CCL21 (C21TP) boosts the signaling of both CCL19 and CCL21. Boosting occurs as a direct consequence of C21TP binding to the CCR7 N-terminus, which seems to free chemokines with basic C-termini from an unfavorable interaction with negatively charged posttranslational modifications in CCR7. Here, we confirm this using a CCL19-variant lacking the basic C-terminus. This variant displays a 22-fold higher potency at CCR7 compared to WT CCL19 and is highly unaffected by the presence of C21TP. WT CCL19 has a short basic C-terminus, CCL21 a longer one. Here, we propose a way to differentially boost CCL19 and CCL21 activity as short and long versions of C21TP boost CCL19 activity, whereas only a long C21TP version can boost chemokines with a full-length CCL21 C-terminus. |
| Databáze: | OpenAIRE |
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