ArticlePLoS computational biology2018
Closely related, yet unique: Distinct homo- and heterodimerization patterns of G protein coupled chemokine receptors and their fine-tuning by cholesterol.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Chemokine receptor activity is differentially regulated by membrane cholesterol.bioRxiv : the preprint server for biology · 2026Article
- Cellular context and ligand class shape CXCR4-CCR5 heteromerization in live cells.Research square · 2026Article
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- Improved Highly Mobile Membrane Mimetic Model for Investigating Protein-Cholesterol Interactions.Journal of chemical information and modeling · 2024Article
- Identifying and Assessing Putative Allosteric Sites and Modulators for CXCR4 Predicted through Network Modeling and Site Identification by Ligand Competitive Saturation.The journal of physical chemistry. B · 2024Article
- Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities.International journal of molecular sciences · 2024Review
- Structural basis of dimerization of chemokine receptors CCR5 and CXCR4.Nature communications · 2023Article
- Entropic barrier of water permeation through single-file channels.Communications chemistry · 2023Article
- Article
- Spontaneous local membrane curvature induced by transmembrane proteins.Biophysical journal · 2022Article
- Evolution of CCR5 and CCR2 Genes in Bats Showed Multiple Independent Gene Conversion Events.Viruses · 2022Article
- ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production.Frontiers in immunology · 2022Article
- Modulation of adenosine A2a receptor oligomerization by receptor activation and PIPStructure (London, England : 1993) · 2021Article
- CXCR4-CCR7 Heterodimerization Is a Driver of Breast Cancer Progression.Life (Basel, Switzerland) · 2021Article
- Computational modeling and experimental validation of the EPI-X4/CXCR4 complex allows rational design of small peptide antagonists.Communications biology · 2021Article
- In Silico Identification of Cholesterol Binding Motifs in the Chemokine Receptor CCR3.Membranes · 2021Article
- Latest update on chemokine receptors as therapeutic targets.Biochemical Society transactions · 2021Review
- Native-like membrane models of E. coli polar lipid extract shed light on the importance of lipid composition complexity.BMC biology · 2021Article
- Lipids and Phosphorylation Conjointly Modulate Complex Formation of βFrontiers in cell and developmental biology · 2021Article
- Cholesterol Is a Dose-Dependent Positive Allosteric Modulator of CCR3 Ligand Affinity and G Protein Coupling.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemokine receptors, a subclass of G protein coupled receptors (GPCRs), play essential roles in the human immune system, they are involved in cancer metastasis as well as in HIV-infection. A plethora of studies show that homo- and heterodimers or even higher order oligomers of the chemokine receptors CXCR4, CCR5, and CCR2 modulate receptor function. In addition, membrane cholesterol affects chemokine receptor activity. However, structural information about homo- and heterodimers formed by chemokine receptors and their interplay with cholesterol is limited. Here, we report homo- and heterodimer configurations of the chemokine receptors CXCR4, CCR5, and CCR2 at atomistic detail, as obtained from thousands of molecular dynamics simulations. The observed homodimerization patterns were similar for the closely related CC chemokine receptors, yet they differed significantly between the CC receptors and CXCR4. Despite their high sequence identity, cholesterol modulated the CC homodimer interfaces in a subtype-specific manner. Chemokine receptor heterodimers display distinct dimerization patterns for CXCR4/CCR5 and CXCR4/CCR2. Furthermore, associations between CXCR4 and CCR5 reveal an increased cholesterol-sensitivity as compared to CXCR4/CCR2 heterodimerization patterns. This work provides a first comprehensive structural overview over the complex interaction network between chemokine receptors and indicates how heterodimerization and the interaction with the membrane environment diversifies the function of closely related GPCRs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.