ArticleThe Journal of biological chemistry2016
CXCL1/MGSA Is a Novel Glycosaminoglycan (GAG)-binding Chemokine: STRUCTURAL EVIDENCE FOR TWO DISTINCT NON-OVERLAPPING BINDING DOMAINS.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- CXCL5: A coachman to drive cancer progression.Frontiers in oncology · 2022Pooled it
- MLK4 orchestrates macrophage-induced triple-negative breast cancer invasion and ECM remodeling via enhanced paracrine signaling and NF-κB-MMP axis activation.Cell death & disease · 2026Article
- Structural Basis of Chemokine CXCL8 Monomer and Dimer Binding to Chondroitin Sulfate: Insights into Specificity and Plasticity.Biomolecules · 2026Article
- The Model of Neutrophil Chemotaxis Participated by the Vascular Endothelial Glycocalyx.International journal of general medicine · 2025Review
- Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant.Journal of leukocyte biology · 2023Article
- Chemokine Heteromers and Their Impact on Cellular Function-A Conceptual Framework.International journal of molecular sciences · 2023Review
- Review
- Review
- Neutrophil recruitment by chemokines Cxcl1/KC and Cxcl2/MIP2: Role of Cxcr2 activation and glycosaminoglycan interactions.Journal of leukocyte biology · 2021Article
- NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins.Frontiers in molecular biosciences · 2021Review
- Tick Saliva Protein Evasin-3 Allows for Visualization of Inflammation in Arteries through Interactions with CXC-Type Chemokines Deposited on Activated Endothelium.Bioconjugate chemistry · 2020Article
- Structural Insights Into How Proteoglycans Determine Chemokine-CXCR1/CXCR2 Interactions: Progress and Challenges.Frontiers in immunology · 2020Review
- Targeting Chemokine-Glycosaminoglycan Interactions to Inhibit Inflammation.Frontiers in immunology · 2020Review
- Structural basis of chemokine interactions with heparan sulfate, chondroitin sulfate, and dermatan sulfate.The Journal of biological chemistry · 2019Article
- How do chemokines navigate neutrophils to the target site: Dissecting the structural mechanisms and signaling pathways.Cellular signalling · 2019Review
- Distribution of bioactive factors in human milk samples.International breastfeeding journal · 2019Article
- Structural basis, stoichiometry, and thermodynamics of binding of the chemokines KC and MIP2 to the glycosaminoglycan heparin.The Journal of biological chemistry · 2018Article
- Article
- Lysines and Arginines play non-redundant roles in mediating chemokine-glycosaminoglycan interactions.Scientific reports · 2018Article
- Directed evolution of broadly crossreactive chemokine-blocking antibodies efficacious in arthritis.Nature communications · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In humans, the chemokine CXCL1/MGSA (hCXCL1) plays fundamental and diverse roles in pathophysiology, from microbial killing to cancer progression, by orchestrating the directed migration of immune and non-immune cells. Cellular trafficking is highly regulated and requires concentration gradients that are achieved by interactions with sulfated glycosaminoglycans (GAGs). However, very little is known regarding the structural basis underlying hCXCL1-GAG interactions. We addressed this by characterizing the binding of GAG heparin oligosaccharides to hCXCL1 using NMR spectroscopy. Binding experiments under conditions at which hCXCL1 exists as monomers and dimers indicate that the dimer is the high-affinity GAG ligand. NMR experiments and modeling studies indicate that lysine and arginine residues mediate binding and that they are located in two non-overlapping domains. One domain, consisting of N-loop and C-helical residues (defined as α-domain) has also been identified previously as the GAG-binding domain for the related chemokine CXCL8/IL-8. The second domain, consisting of residues from the N terminus, 40s turn, and third β-strand (defined as β-domain) is novel. Eliminating β-domain binding by mutagenesis does not perturb α-domain binding, indicating two independent GAG-binding sites. It is known that N-loop and N-terminal residues mediate receptor activation, and we show that these residues are also involved in extensive GAG interactions. We also show that the GAG-bound hCXCL1 completely occlude receptor binding. We conclude that hCXCL1-GAG interactions provide stringent control over regulating chemokine levels and receptor accessibility and activation, and that chemotactic gradients mediate cellular trafficking to the target site.
Indexed as
Identifiers
What OpenQuestion holds
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.