Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5
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Inflammatory chemokines are often elevated in disease settings, where the largest group of CC-chemokines are the macrophage inflammatory proteins (MIP), which are promiscuous for the receptors CCR1 and CCR5. MIP chemokines, such as CCL3 and CCL5 are processed at the N terminus, which influences signaling in a highly diverse manner. Here, we investigate the signaling capacity of peptides corresponding to truncated N termini. These 3–10-residue peptides displayed weak potency but, surprisingly, retained their signaling on CCR1. In contrast, none of the peptides generated a signal on CCR5, but a CCL3-derived tetrapeptide was a positive modulator boosting the signal of several chemokine variants on CCR5. In conclusion, chemokine N termini can be mimicked to produce small CCR1-selective agonists, as well as CCR5-selective modulators.
Original language | English |
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Journal | FEBS Letters |
Volume | 597 |
Issue number | 24 |
Pages (from-to) | 3049-3060 |
ISSN | 0014-5793 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
© 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
- allosteric modulation, chemokine, chemokine truncation, GPCR, pharmacology
Research areas
ID: 377451683