Bilayer lipids modulate ligand binding to atypical chemokine receptor 3

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

Standard

Bilayer lipids modulate ligand binding to atypical chemokine receptor 3. / Eberle, Stefanie Alexandra; Gustavsson, Martin.

In: Structure, 2024.

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

Harvard

Eberle, SA & Gustavsson, M 2024, 'Bilayer lipids modulate ligand binding to atypical chemokine receptor 3', Structure. https://doi.org/10.1016/j.str.2024.04.018

APA

Eberle, S. A., & Gustavsson, M. (2024). Bilayer lipids modulate ligand binding to atypical chemokine receptor 3. Structure. https://doi.org/10.1016/j.str.2024.04.018

Vancouver

Eberle SA, Gustavsson M. Bilayer lipids modulate ligand binding to atypical chemokine receptor 3. Structure. 2024. https://doi.org/10.1016/j.str.2024.04.018

Author

Eberle, Stefanie Alexandra ; Gustavsson, Martin. / Bilayer lipids modulate ligand binding to atypical chemokine receptor 3. In: Structure. 2024.

Bibtex

@article{25cf39feee764db395c8f3f68457c955,
title = "Bilayer lipids modulate ligand binding to atypical chemokine receptor 3",
abstract = "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.",
keywords = "ACKR3, chemokine, chemokine receptor, CXCL12, CXCR7, G protein-coupled receptor, GPCR, kinetic, lipid, membrane",
author = "Eberle, {Stefanie Alexandra} and Martin Gustavsson",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2024",
doi = "10.1016/j.str.2024.04.018",
language = "English",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",

}

RIS

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