ArticleThe Journal of biological chemistry2013
Molecular basis of glycosaminoglycan heparin binding to the chemokine CXCL1 dimer.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023Review
- Prospects for targeting ACKR1 in cancer and other diseases.Frontiers in immunology · 2023Review
- Heparan sulfates and heparan sulfate binding proteins in sepsis.Frontiers in molecular biosciences · 2023Review
- Review
- 3-Computational and structural biotechnology journal · 2022Article
- Neutrophil recruitment by chemokines Cxcl1/KC and Cxcl2/MIP2: Role of Cxcr2 activation and glycosaminoglycan interactions.Journal of leukocyte biology · 2021Article
- 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
- Interleukin-37 monomer is the active form for reducing innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structural basis, stoichiometry, and thermodynamics of binding of the chemokines KC and MIP2 to the glycosaminoglycan heparin.The Journal of biological chemistry · 2018Article
- Glycosaminoglycan-Protein Interactions by Nuclear Magnetic Resonance (NMR) Spectroscopy.Molecules (Basel, Switzerland) · 2018Review
- Glycosaminoglycan Interactions Fine-Tune Chemokine-Mediated Neutrophil Trafficking: Structural Insights and Molecular Mechanisms.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Review
- The Role of Heparan Sulfate in Inflammation, and the Development of Biomimetics as Anti-Inflammatory Strategies.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Review
- Heparin-bound chemokine CXCL8 monomer and dimer are impaired for CXCR1 and CXCR2 activation: implications for gradients and neutrophil trafficking.Open biology · 2017Article
- Mechanistic insights into molecular evolution of species-specific differential glycosaminoglycan binding surfaces in growth-related oncogene chemokines.Royal Society open science · 2017Article
- Regulation of Chemokine Function: The Roles of GAG-Binding and Post-Translational Nitration.International journal of molecular sciences · 2017Review
- Modulation of Interleukin-12 activity in the presence of heparin.Scientific reports · 2017Article
- Platelet-Derived Chemokine CXCL7 Dimer Preferentially Exists in the Glycosaminoglycan-Bound Form: Implications for Neutrophil-Platelet Crosstalk.Frontiers in immunology · 2017Article
- Molecular Basis of Chemokine CXCL5-Glycosaminoglycan Interactions.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glycosaminoglycan (GAG)-bound and soluble chemokine gradients in the vasculature and extracellular matrix mediate neutrophil recruitment to the site of microbial infection and sterile injury in the host tissue. However, the molecular principles by which chemokine-GAG interactions orchestrate these gradients are poorly understood. This, in part, can be directly attributed to the complex interrelationship between the chemokine monomer-dimer equilibrium and binding geometry and affinities that are also intimately linked to GAG length. To address some of this missing knowledge, we have characterized the structural basis of heparin binding to the murine CXCL1 dimer. CXCL1 is a neutrophil-activating chemokine and exists as both monomers and dimers (Kd = 36 μm). To avoid interference from monomer-GAG interactions, we designed a trapped dimer (dCXCL1) by introducing a disulfide bridge across the dimer interface. We characterized the binding of GAG heparin octasaccharide to dCXCL1 using solution NMR spectroscopy. Our studies show that octasaccharide binds orthogonally to the interhelical axis and spans the dimer interface and that heparin binding enhances the structural integrity of the C-terminal helical residues and stability of the dimer. We generated a quadruple mutant (H20A/K22A/K62A/K66A) on the basis of the binding data and observed that this mutant failed to bind heparin octasaccharide, validating our structural model. We propose that the stability enhancement of dimers upon GAG binding regulates in vivo neutrophil trafficking by increasing the lifetime of "active" chemokines, and that this structural knowledge could be exploited for designing inhibitors that disrupt chemokine-GAG interactions and neutrophil homing to the target tissue.
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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.