Differential activity and selectivity of N‐terminal modified CXCL12 chemokines at the CXCR4 and ACKR3 receptors

Agnieszka Jaracz-Ros (1) , Guillaume Bernadat (2) , Pasquale Cutolo (1) , Carmen Gallego (1) , Martin Gustavsson (3) , Erika Cecon (4) , Françoise Baleux (5) , Irina Kufareva (3) , Tracy M Handel (3) , Françoise Bachelerie (1) , Angélique Levoye (6, 7)

1 MI2 - Inflammation, microbiome, immunosurveillance
2 BioCIS - Biomolécules : Conception, Isolement, Synthèse
3 Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego]
4 IC UM3 (UMR 8104 / U1016) - Institut Cochin
5 Chimie des Biomolécules - Chemistry of Biomolecules
6 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
7 Université Sorbonne Paris Nord

Chemokines play critical roles in numerous physiological and pathological processes through their action on seven-transmembrane (TM) receptors. The N-terminal domain of chemokines, which is a key determinant of signaling via its binding within a pocket formed by receptors' TM helices, can be the target of proteolytic processing. An illustrative case of this regulatory mechanism is the natural processing of CXCL12 that generates chemokine variants lacking the first two N-terminal residues. While such truncated variants behave as antagonists of CXCR4, the canonical G proteincoupled receptor of CXCL12, they are agonists of the atypical chemokine receptor 3 (ACKR3/

Keywords: ACKR3; CXCR4; CXCL12; chemokine variants; GPCR signaling; pluridimensional efficacy Receptors; Signal Transduction and Genes; pluridimensional efficacy

Domains: Life Sciences [q-bio]

Agnieszka Jaracz-Ros, Guillaume Bernadat, Pasquale Cutolo, Carmen Gallego, Martin Gustavsson, et al.. Differential activity and selectivity of N‐terminal modified CXCL12 chemokines at the CXCR4 and ACKR3 receptors. Journal of Leukocyte Biology, 2020, 107 (6), pp.1123 - 1135. ⟨10.1002/jlb.2ma0320-383rr⟩. ⟨pasteur-03260272⟩