ArticleProceedings of the National Academy of Sciences of the United States of America2016
Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
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- Periodic asymmetric field enhances electrofusion of nanoscale lipid systems.Nature communications · 2025Article
- CXCR4 mediated recognition of HIV envelope spike and inhibition by CXCL12.Nature communications · 2025Article
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
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- Structural insights into CXCR4 modulation and oligomerization.Nature structural & molecular biology · 2025Article
- Interaction and dynamics of chemokine receptor CXCR4 binding with CXCL12 and hBD-3.Communications chemistry · 2024Article
- Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain.eLife · 2024Article
- Secretory Trefoil Factor 1 (TFF1) promotes gemcitabine resistance through chemokine receptor CXCR4 in Pancreatic Ductal Adenocarcinoma.Cancer letters · 2024Article
- G protein-coupled receptors and traditional Chinese medicine: new thinks for the development of traditional Chinese medicine.Chinese medicine · 2024Review
- The role of lidocaine in cancer progression and patient survival.Pharmacology & therapeutics · 2024Review
- 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
- The β2-adrenergic receptor associates with CXCR4 multimers in human cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pathological progression of osteoarthritis: a perspective on subchondral bone.Frontiers of medicine · 2024Review
- CXCR4 Is a Potential Target for Anti-HIV Gene Therapy.International journal of molecular sciences · 2024Review
- The complex nature of CXCR4 mutations in WHIM syndrome.Frontiers in immunology · 2024Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The atomic-level mechanisms by which G protein-coupled receptors (GPCRs) transmit extracellular ligand binding events through their transmembrane helices to activate intracellular G proteins remain unclear. Using a comprehensive library of mutations covering all 352 residues of the GPCR CXC chemokine receptor 4 (CXCR4), we identified 41 amino acids that are required for signaling induced by the chemokine ligand CXCL12 (stromal cell-derived factor 1). CXCR4 variants with each of these mutations do not signal properly but remain folded, based on receptor surface trafficking, reactivity to conformationally sensitive monoclonal antibodies, and ligand binding. When visualized on the structure of CXCR4, the majority of these residues form a continuous intramolecular signaling chain through the transmembrane helices; this chain connects chemokine binding residues on the extracellular side of CXCR4 to G protein-coupling residues on its intracellular side. Integrated into a cohesive model of signal transmission, these CXCR4 residues cluster into five functional groups that mediate (i) chemokine engagement, (ii) signal initiation, (iii) signal propagation, (iv) microswitch activation, and (v) G protein coupling. Propagation of the signal passes through a "hydrophobic bridge" on helix VI that coordinates with nearly every known GPCR signaling motif. Our results agree with known conserved mechanisms of GPCR activation and significantly expand on understanding the structural principles of CXCR4 signaling.
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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.