Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5. / Larsen, Olav; Schuermans, Sara; Walser, Anna; Louka, Stavroula; Lillethorup, Ida Aaberg; Våbenø, Jon; Qvortrup, Katrine; Proost, Paul; Rosenkilde, Mette M.

In: FEBS Letters, Vol. 597, No. 24, 2023, p. 3049-3060.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Larsen, O, Schuermans, S, Walser, A, Louka, S, Lillethorup, IA, Våbenø, J, Qvortrup, K, Proost, P & Rosenkilde, MM 2023, 'Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5', FEBS Letters, vol. 597, no. 24, pp. 3049-3060. https://doi.org/10.1002/1873-3468.14778

APA

Larsen, O., Schuermans, S., Walser, A., Louka, S., Lillethorup, I. A., Våbenø, J., Qvortrup, K., Proost, P., & Rosenkilde, M. M. (2023). Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5. FEBS Letters, 597(24), 3049-3060. https://doi.org/10.1002/1873-3468.14778

Vancouver

Larsen O, Schuermans S, Walser A, Louka S, Lillethorup IA, Våbenø J et al. Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5. FEBS Letters. 2023;597(24):3049-3060. https://doi.org/10.1002/1873-3468.14778

Author

Larsen, Olav ; Schuermans, Sara ; Walser, Anna ; Louka, Stavroula ; Lillethorup, Ida Aaberg ; Våbenø, Jon ; Qvortrup, Katrine ; Proost, Paul ; Rosenkilde, Mette M. / Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5. In: FEBS Letters. 2023 ; Vol. 597, No. 24. pp. 3049-3060.

Bibtex

@article{22877af8bb034bfdbe0bad5ee75e4221,
title = "Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5",
abstract = "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.",
keywords = "allosteric modulation, chemokine, chemokine truncation, GPCR, pharmacology",
author = "Olav Larsen and Sara Schuermans and Anna Walser and Stavroula Louka and Lillethorup, {Ida Aaberg} and Jon V{\aa}ben{\o} and Katrine Qvortrup and Paul Proost and Rosenkilde, {Mette M.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.",
year = "2023",
doi = "10.1002/1873-3468.14778",
language = "English",
volume = "597",
pages = "3049--3060",
journal = "F E B S Letters",
issn = "0014-5793",
publisher = "JohnWiley & Sons Ltd",
number = "24",

}

RIS

TY - JOUR

T1 - Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5

AU - Larsen, Olav

AU - Schuermans, Sara

AU - Walser, Anna

AU - Louka, Stavroula

AU - Lillethorup, Ida Aaberg

AU - Våbenø, Jon

AU - Qvortrup, Katrine

AU - Proost, Paul

AU - Rosenkilde, Mette M.

N1 - Publisher Copyright: © 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - allosteric modulation

KW - chemokine

KW - chemokine truncation

KW - GPCR

KW - pharmacology

U2 - 10.1002/1873-3468.14778

DO - 10.1002/1873-3468.14778

M3 - Journal article

C2 - 37994578

AN - SCOPUS:85178910309

VL - 597

SP - 3049

EP - 3060

JO - F E B S Letters

JF - F E B S Letters

SN - 0014-5793

IS - 24

ER -

ID: 377451683