ArticleScientific reports2018
Identification of an Arg-Leu-Arg tripeptide that contributes to the binding interface between the cytokine MIF and the chemokine receptor CXCR4.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed, 47 citations in OpenAlex.
- Helminth proteins recapitulate key structural motifs of MIF to facilitate immunomodulation of host receptors.iScience · 2026Article
- Distinctive Macrophage Migration Inhibitory Factor Receptor Patterns and Soluble Biomarkers in Rheumatoid Arthritis: Unveiling Key Associations with Disease Activity.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Targeting immune cell recruitment in atherosclerosis.Nature reviews. Cardiology · 2024Review
- Article
- Hallmarks of Cancer Affected by the MIF Cytokine Family.Cancers · 2023Review
- Heterocomplexes between the atypical chemokine MIF and the CXC-motif chemokine CXCL4L1 regulate inflammation and thrombus formation.Cellular and molecular life sciences : CMLS · 2022Article
- Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma.Cell death & disease · 2022Article
- Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury.Cellular and molecular life sciences : CMLS · 2022Review
- A Cysteine Variant at an Allosteric Site Alters MIF Dynamics and Biological Function in Homo- and Heterotrimeric Assemblies.Frontiers in molecular biosciences · 2022Article
- Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR.Journal of clinical medicine · 2021Article
- A MIF-Derived Cyclopeptide that Inhibits MIF Binding and Atherogenic Signaling via the Chemokine Receptor CXCR2.Chembiochem : a European journal of chemical biology · 2021Article
- Chemokines in Myocardial Infarction.Journal of cardiovascular translational research · 2021Review
- CXCL12 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Review
- Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting.Nature communications · 2020Article
- mRNA Expression Profiles from Whole Blood Associated with Vasospasm in Patients with Subarachnoid Hemorrhage.Neurocritical care · 2020Article
- Kinetic Analysis of the Early Signaling Steps of the Human Chemokine Receptor CXCR4.Molecular pharmacology · 2020Article
- The Human Host-Defense Peptide Cathelicidin LL-37 is a Nanomolar Inhibitor of Amyloid Self-Assembly of Islet Amyloid Polypeptide (IAPP).Angewandte Chemie (International ed. in English) · 2020Article
- Regulation of MIF Enzymatic Activity by an Allosteric Site at the Central Solvent Channel.Cell chemical biology · 2020Article
- Cross-kingdom mimicry of the receptor signaling and leukocyte recruitment activity of a human cytokine by its plant orthologs.The Journal of biological chemistry · 2020Article
- CD74 Signaling Links Inflammation to Intestinal Epithelial Cell Regeneration and Promotes Mucosal Healing.Cellular and molecular gastroenterology and hepatology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
MIF is a chemokine-like cytokine that plays a role in the pathogenesis of inflammatory and cardiovascular disorders. It binds to the chemokine-receptors CXCR2/CXCR4 to trigger atherogenic leukocyte migration albeit lacking canonical chemokine structures. We recently characterized an N-like-loop and the Pro-2-residue of MIF as critical molecular determinants of the CXCR4/MIF binding-site and identified allosteric agonism as a mechanism that distinguishes CXCR4-binding to MIF from that to the cognate ligand CXCL12. By using peptide spot-array technology, site-directed mutagenesis, structure-activity-relationships, and molecular docking, we identified the Arg-Leu-Arg (RLR) sequence-region 87-89 that - in three-dimensional space - 'extends' the N-like-loop to control site-1-binding to CXCR4. Contrary to wildtype MIF, mutant R87A-L88A-R89A-MIF fails to bind to the N-terminal of CXCR4 and the contribution of RLR to the MIF/CXCR4-interaction is underpinned by an ablation of MIF/CXCR4-specific signaling and reduction in CXCR4-dependent chemotactic leukocyte migration of the RLR-mutant of MIF. Alanine-scanning, functional competition by RLR-containing peptides, and molecular docking indicate that the RLR residues directly participate in contacts between MIF and CXCR4 and highlight the importance of charge-interactions at this interface. Identification of the RLR region adds important structural information to the MIF/CXCR4 binding-site that distinguishes this interface from CXCR4/CXCL12 and will help to design MIF-specific drug-targeting approaches.
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.