ArticleProceedings of the National Academy of Sciences of the United States of America2013
Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.
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 275 papers.
What it found
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Who cites it
275 citing papers in PubMed, 390 citations in OpenAlex.
- A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus.Nucleic acids research · 2026Article
- Formation of the intradimer disulfide bond in human calprotectin maintains metal-withholding function and tunes proteolytic susceptibility.Chemical science · 2026Article
- Article
- The intestinal microbiota impacts nutritional immunity and resistance toProceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Abundance Paradox of S100A8/A9 in Neutrophils: Functional Logic of Calprotectin Dominance in the Cytosolic Proteome.International journal of molecular sciences · 2026Review
- Metal-independent effects of calprotectin on cocultures ofbioRxiv : the preprint server for biology · 2026Article
- Article
- Mechanisms and Therapeutic Potential of Nutritional Immunity.Pathogens (Basel, Switzerland) · 2026Review
- Structural insights into zinc piracy by Neisseria gonorrhoeae to overcome nutritional immunity.Structure (London, England : 1993) · 2026Article
- Deletion ofApplied and environmental microbiology · 2026Article
- The innate immune protein calprotectin ablates the bactericidal activity of β-lactam antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ExploitingFrontiers in immunology · 2026Article
- Design and characterization of calprotectin tetramerization variants for probing the role of oligomerization in receptor activation.Protein science : a publication of the Protein Society · 2026Article
- Targeting S100A8/A9: a molecular gateway to oral inflammation, microglial activation and neuroinflammation.Frontiers in immunology · 2026Review
- pH-triggered Mn-ZIF8 nanoreactor enhances tumor immunotherapy by amplifying the cGAS-STING pathway through a self-reinforcing gas-metal synergy strategy.Journal of nanobiotechnology · 2025Article
- Cervicovaginal microbiome alters transcriptomic and chromatin accessibility signatures across cervicovaginal epithelial barriers.Microbiome · 2025Article
- Exploring Metalloproteome Remodeling in Calprotectin-StressedACS chemical biology · 2025Article
- Forging biofilms: metal-induced microbial responses in biofilm formation.Journal of bacteriology · 2025Review
- Integrated Transcriptomic Analysis of S100A8/A9 as a Key Biomarker and Therapeutic Target in Sepsis Pathogenesis and AI Drug Repurposing.International journal of molecular sciences · 2025Article
- Molecular Basis of Calcium-Induced Acidic Shift in Antimicrobial Zinc Sequestration by S100A12.The journal of physical chemistry. B · 2025Article
215 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
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn(2+) sequestration. The asymmetry of the CP heterodimer creates a single Mn(2+)-binding site from six histidine residues, which distinguishes CP from all other Mn(2+)-binding proteins. Analysis of CP mutants with altered metal-binding properties revealed that, despite both Mn(2+) and Zn(2+) being essential metals, maximal growth inhibition of multiple bacterial pathogens requires Mn(2+) sequestration. These data establish the importance of Mn(2+) sequestration in defense against infection, explain the broad-spectrum antimicrobial activity of CP relative to other S100 proteins, and clarify the impact of metal depletion on the innate immune response to infection.
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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.