Bilayer lipids modulate ligand binding to atypical chemokine receptor 3
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Bilayer lipids modulate ligand binding to atypical chemokine receptor 3. / Eberle, Stefanie Alexandra; Gustavsson, Martin.
I: Structure, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Bilayer lipids modulate ligand binding to atypical chemokine receptor 3
AU - Eberle, Stefanie Alexandra
AU - Gustavsson, Martin
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024
Y1 - 2024
N2 - Chemokine receptors belong to the large class of G protein-coupled receptors (GPCRs) and are involved in a number of (patho)physiological processes. Previous studies highlighted the importance of membrane lipids for modulating GPCR structure and function. However, the underlying mechanisms of how lipids regulate GPCRs are often poorly understood. Here, we report that anionic lipid bilayers increase the binding affinity of the chemokine CXCL12 for the atypical chemokine receptor 3 (ACKR3) by modulating the CXCL12 binding kinetics. Notably, the anionic bilayer favors CXCL12 over the more positively charged chemokine CXCL11, which we explained by bilayer interactions orienting CXCL12 but not CXCL11 for productive ACKR3 binding. Furthermore, our data suggest a stabilization of active ACKR3 conformations in anionic bilayers. Taken together, the described regulation of chemokine selectivity of ACKR3 by the lipid bilayer proposes an extended version of the classical model of chemokine binding including the lipid environment of the receptor.
AB - Chemokine receptors belong to the large class of G protein-coupled receptors (GPCRs) and are involved in a number of (patho)physiological processes. Previous studies highlighted the importance of membrane lipids for modulating GPCR structure and function. However, the underlying mechanisms of how lipids regulate GPCRs are often poorly understood. Here, we report that anionic lipid bilayers increase the binding affinity of the chemokine CXCL12 for the atypical chemokine receptor 3 (ACKR3) by modulating the CXCL12 binding kinetics. Notably, the anionic bilayer favors CXCL12 over the more positively charged chemokine CXCL11, which we explained by bilayer interactions orienting CXCL12 but not CXCL11 for productive ACKR3 binding. Furthermore, our data suggest a stabilization of active ACKR3 conformations in anionic bilayers. Taken together, the described regulation of chemokine selectivity of ACKR3 by the lipid bilayer proposes an extended version of the classical model of chemokine binding including the lipid environment of the receptor.
KW - ACKR3
KW - chemokine
KW - chemokine receptor
KW - CXCL12
KW - CXCR7
KW - G protein-coupled receptor
KW - GPCR
KW - kinetic
KW - lipid
KW - membrane
UR - http://www.scopus.com/inward/record.url?scp=85195380153&partnerID=8YFLogxK
U2 - 10.1016/j.str.2024.04.018
DO - 10.1016/j.str.2024.04.018
M3 - Journal article
C2 - 38776922
AN - SCOPUS:85195380153
JO - Structure
JF - Structure
SN - 0969-2126
ER -
ID: 394988118