Characterization of a chimeric chemokine as a specific ligand for ACKR3

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Rafet Ameti¹  Serena Melgrati¹  Egle Radice¹  Elisabetta Cameroni¹  Elin Hub⁴  Sylvia Thelen¹  Antal Rot⁴  Marcus Thelen¹ 

[1] Institute for Research in Biomedicine Università della Svizzera italiana Bellinzona Switzerland;University of York, York, United Kingdom;Graduate School for Cellular and Biomedical Sciences University of Bern Bern Switzerland;The William Harvey Research Institute Queen Mary University London London United Kingdom;Institute for Cardiovascular Prevention Ludwig‐Maximilians University (LMU) Munich Germany

关键词: Chemokine;    chemokine receptor;    ACKR3;    synthetic chemokine;   

DOI  :  10.1002/JLB.2MA1217-509R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Chemokines, small chemotactic cytokines, orchestrate cell migration by binding to their cognate chemokine receptors. While chemokine‐mediated stimulation of typical G‐protein‐coupled chemokine receptors leads to cell migration, binding of chemokines to atypical chemokine receptors (ACKRs) does not induce canonical signaling. ACKRs are considered important chemokine scavengers, that can create gradients which help direct cells to sites of inflammation or to their immunological niches. Synthetic chemokines have been used in the past to study and decode chemokine‐receptor interactions. Characterizing specific chemokine‐ACKRs interactions is challenging because the chemokines bind multiple receptors; for example, the ACKR3 ligands CXCL12 and CXCL11 bind to the canonical receptors CXCR4 and CXCR3, respectively. Here, we present the engineering of a chemokine‐like chimera, which selectively binds to ACKR3. The addition of a ybbR13 tag at the C‐terminus allows site specific enzymatic labeling with a plethora of fluorescent dyes. The chimera is composed of the N‐terminus of CXCL11 and the main body and C‐terminus of CXCL12 and selectively interacts with ACKR3 with high affinity, while not interfering with binding of CXCL11 and CXCL12 to their cognate receptors. We further provide evidence that the chimera can be used to study ACKR3 function in vivo.

【 授权许可】

CC BY