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.
Originalsprog | Engelsk |
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Tidsskrift | FEBS Letters |
Vol/bind | 597 |
Udgave nummer | 24 |
Sider (fra-til) | 3049-3060 |
ISSN | 0014-5793 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This study was supported by the European Research Council: VIREX (grant agreement 682549, call ERC‐2105‐CoG), the Lundbeck Foundation (R268‐2017‐409) and a C1 grant from KU Leuven (C16/17/010). SS is supported by a PhD fellowship from FWO‐Vlaanderen (1116922 N).
Publisher Copyright:
© 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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