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 languageEnglish
JournalFEBS Letters
Issue number24
Pages (from-to)3049-3060
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

    Research areas

  • allosteric modulation, chemokine, chemokine truncation, GPCR, pharmacology

ID: 377451683