Poster (Scientific congresses and symposiums)
The atypical chemokine receptor ACKR3/CXCR7 displays distinct binding and activation modes for its endogenous agonists
Meyrath, Max Marc Roger; Szpakowska, Martyna; Counson, Manuel et al.
2017Luxembourg Life Sciences PhD Days 2017
 

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Keywords :
Chemokine receptor; ACKR3; ligand binding; N-terminus; CXCR4; beta-arrestin
Abstract :
[en] Background The atypical chemokine receptor ACKR3, formerly CXCR7, binds the endogenous chemokines CXCL12 and CXCL11, as well as the virus-encoded chemokine vCCL2. ACKR3 is crucially involved in various physiological processes but also in viral infection and cancer development, making it a promising drug target, yet a potent antagonist for this receptor is still lacking. Acting as a scavenging receptor, ACKR3 internalizes chemokines without activating the canonical G-protein signaling. ACKR3 extracellular domains present three disulfide bridges, two being conserved among chemokine receptors and one being exclusive to ACKR3, forming a four-residue loop of so far unknown function in the receptors’ N terminus. Goal Investigate the impact of extracellular disulfide bridges on surface expression, ligand binding and activation of ACKR3 in comparison to CXCR4, the second receptor for CXCL12 Approach Creation of C to S mutants, breaking all three disulfide bridges present in ACKR3 1) Connecting the N terminus with ECL3 (present in all chemokine receptors) (C34S-C287S) 2) Bridging ECL1 and ECL2, (present in all G protein-coupled receptors) (C117S-C196S) 3) Forming a four-residue loop in the N terminus (unique for ACKR3) (C21S –C26S) And creation of a 4th mutant: four internal residues of the N-terminal loop to glycine (C21-G4-C26)
Research center :
Luxembourg Institute of Health
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Meyrath, Max Marc Roger ;  Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (paysage)
Szpakowska, Martyna;  Luxembourg Institute of Health
Counson, Manuel;  Luxembourg Institute of Health
Reynders, Nathan
Julien, Hanson
Ollert, Markus
Chevigné, Andy;  Luxembourg Institute of Health
Language :
English
Title :
The atypical chemokine receptor ACKR3/CXCR7 displays distinct binding and activation modes for its endogenous agonists
Publication date :
December 2017
Event name :
Luxembourg Life Sciences PhD Days 2017
Event organizer :
University of Luxembourg
Event date :
07-12-2017 to 08-12-2017
Name of the research project :
AFR program (PseudoKINE, ref #11274579)
Funders :
FNR - Fonds National de la Recherche [LU]
Available on ORBi :
since 14 June 2018

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