Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake

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2022
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Cells. MDPI. 2022, 11(9), 1444. eISSN 2073-4409. Available under: doi: 10.3390/cells11091444
Zusammenfassung

The chemokine receptor CCR7, together with its ligands, is responsible for the migration and positioning of adaptive immune cells, and hence critical for launching adaptive immune responses. CCR7 is also induced on certain cancer cells and contributes to metastasis formation. Thus, CCR7 expression and signalling must be tightly regulated for proper function. CCR7, like many other members of the G-protein coupled receptor superfamily, can form homodimers and oligomers. Notably, danger signals associated with pathogen encounter promote oligomerisation of CCR7 and is considered as one layer of regulating its function. Here, we assessed the dimerisation of human CCR7 and several single point mutations using split-luciferase complementation assays. We demonstrate that dimerisation-defective CCR7 mutants can be transported to the cell surface and elicit normal chemokine-driven G-protein activation. By contrast, we discovered that CCR7 mutants whose expression are shifted towards monomers significantly augment their capacities to bind and internalise fluorescently labelled CCL19. Modeling of the receptor suggests that dimerisation-defective CCR7 mutants render the extracellular loops more flexible and less structured, such that the chemokine recognition site located in the binding pocket might become more accessible to its ligand. Overall, we provide new insights into how the dimerisation state of CCR7 affects CCL19 binding and receptor trafficking.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
chemokine receptor CCR7; receptor dimerisation; receptor trafficking; chemokine binding; signalling; GPCR
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ISO 690GERKEN, Oliver J., Marc ARTINGER, Daniel F. LEGLER, 2022. Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake. In: Cells. MDPI. 2022, 11(9), 1444. eISSN 2073-4409. Available under: doi: 10.3390/cells11091444
BibTex
@article{Gerken2022-05Shift-57506,
  year={2022},
  doi={10.3390/cells11091444},
  title={Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake},
  number={9},
  volume={11},
  journal={Cells},
  author={Gerken, Oliver J. and Artinger, Marc and Legler, Daniel F.},
  note={Article Number: 1444}
}
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