ArticleProceedings of the National Academy of Sciences of the United States of America2013
MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. 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
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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
27 citing papers in PubMed, 45 citations in OpenAlex.
- Atomistic modulation of MIF-2 structure, catalysis, and biological signaling via cysteine residues and a small molecule, Ebselen.Protein science : a publication of the Protein Society · 2025Article
- HumanTestisDB: A Comprehensive Atlas of Testicular Transcriptomes and Cellular Interactions.Genomics, proteomics & bioinformatics · 2025Article
- Infliximab modifies CD74-mediated lymphatic abnormalities and adipose tissue alterations in creeping fat of Crohn's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.Cell reports. Medicine · 2024Article
- Single-Cell RNA-Seq Analysis Reveals Macrophages Are Involved in the Pathogenesis of Human Sporadic Acute Type A Aortic Dissection.Biomolecules · 2023Article
- Treatment with an antigen-specific dual microparticle system reverses advanced multiple sclerosis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Heterocomplexes between the atypical chemokine MIF and the CXC-motif chemokine CXCL4L1 regulate inflammation and thrombus formation.Cellular and molecular life sciences : CMLS · 2022Article
- MIF homolog d-dopachrome tautomerase (D-DT/MIF-2) does not inhibit accumulation and toxicity of misfolded SOD1.Scientific reports · 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
- Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function.Frontiers in molecular biosciences · 2021Review
- Article
- Macrophage migration inhibitory factor is involved in antineutrophil cytoplasmic antibody-mediated activation of C5a-primed neutrophils.BMC immunology · 2019Article
- Article
- Advances and Insights for Small Molecule Inhibition of Macrophage Migration Inhibitory Factor.Journal of medicinal chemistry · 2018Article
- Identification of an Arg-Leu-Arg tripeptide that contributes to the binding interface between the cytokine MIF and the chemokine receptor CXCR4.Scientific reports · 2018Article
- MIF inhibits the formation and toxicity of misfolded SOD1 amyloid aggregates: implications for familial ALS.Cell death & disease · 2018Article
- Cell Signaling with Extracellular Thioredoxin and Thioredoxin-Like Proteins: Insight into Their Mechanisms of Action.Oxidative medicine and cellular longevity · 2017Review
- Structural basis for decreased induction of class IB PI3-kinases expression by MIF inhibitors.Journal of cellular and molecular medicine · 2017Article
- Modeling of both shared and distinct interactions between MIF and its homologue D-DT with their common receptor CD74.Cytokine · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. In addition to its known receptor-mediated biological activities, MIF possesses a catalytic site of unknown function between subunits of a homotrimer. Each subunit contributes three β-strands to adjacent subunits to form a core seven-stranded β-sheet for each monomer. MIF monomers, dimers, or trimers have been reported, but the active form that binds and activates the MIF receptor (CD74) is still a matter of debate. A cysteine mutant (N110C) that covalently locks MIF into a trimer by forming a disulfide with Cys-80 of an adjacent subunit is used to study this issue. Partial catalytic activity and receptor binding to CD74 are retained by N110C (locked trimer), but there is no cellular signaling. Wild-type MIF-induced cellular signaling, in vivo lung neutrophil accumulation, and alveolar permeability are inhibited with a fivefold excess of N110C. NMR and size-exclusion chromatography with light scattering reveal that N110C can form a higher-order oligomer in equilibrium with a single locked trimer. The X-ray structure confirms a local conformational change that disrupts the subunit interface and results in global changes responsible for the oligomeric form. The structure also confirms these changes are consistent for the partial catalytic and receptor binding activities. The absence of any potential monomer and the retention of partial catalytic and receptor binding activities despite changes in conformation (and dynamics) in the mutant support an endogenous MIF trimer that binds and activates CD74 at nanomolar concentrations. This conclusion has implications for therapeutic development.
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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.