ArticlePloS one2016
Multiple Evolutionary Origins of Ubiquitous Cu2+ and Zn2+ Binding in the S100 Protein Family.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 37 citations in OpenAlex.
- The Role of Alarmins in the Pathogenesis of Asthma.Biomolecules · 2025Review
- Zebrafish do not have a calprotectin ortholog.PloS one · 2025Article
- A review on clinical implications of S100 proteins in lung diseases.Frontiers in medicine · 2025Review
- Changing expression system alters oligomerization and proinflammatory activity of recombinant human S100A9.bioRxiv : the preprint server for biology · 2024Article
- The Role of Alarmins in the Pathogenesis of Rheumatoid Arthritis, Osteoarthritis, and Psoriasis.Current issues in molecular biology · 2024Review
- Eye lens β-crystallins are predicted by native ion mobility-mass spectrometry and computations to form compact higher-ordered heterooligomers.Structure (London, England : 1993) · 2023Article
- Review
- A Structural Perspective on Calprotectin as a Ligand of Receptors Mediating Inflammation and Potential Drug Target.Biomolecules · 2022Review
- Mechanism of ZnBiomolecules · 2021Article
- Lipid Head Group Adduction to Soluble Proteins Follows Gas-Phase Basicity Predictions: Dissociation Barriers and Charge Abstraction.International journal of mass spectrometry · 2021Article
- The dynein light chain 8 (LC8) binds predominantly "in-register" to a multivalent intrinsically disordered partner.The Journal of biological chemistry · 2020Article
- Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9.eLife · 2020Article
- Avian MRP126 Restricts Microbial Growth through Ca(II)-Dependent Zn(II) Sequestration.Biochemistry · 2020Article
- Computational Insights into Compaction of Gas-Phase Protein and Protein Complex Ions in Native Ion Mobility-Mass Spectrometry.Trends in analytical chemistry : TRAC · 2019Article
- pytc: Open-Source Python Software for Global Analyses of Isothermal Titration Calorimetry Data.Biochemistry · 2018Article
- Conservation of Specificity in Two Low-Specificity Proteins.Biochemistry · 2018Article
- Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide.Frontiers in immunology · 2018Article
- Human S100A5 binds CaBMC biophysics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The S100 proteins are a large family of signaling proteins that play critical roles in biology and disease. Many S100 proteins bind Zn2+, Cu2+, and/or Mn2+ as part of their biological functions; however, the evolutionary origins of binding remain obscure. One key question is whether divalent transition metal binding is ancestral, or instead arose independently on multiple lineages. To tackle this question, we combined phylogenetics with biophysical characterization of modern S100 proteins. We demonstrate an earlier origin for established S100 subfamilies than previously believed, and reveal that transition metal binding is widely distributed across the tree. Using isothermal titration calorimetry, we found that Cu2+ and Zn2+ binding are common features of the family: the full breadth of human S100 paralogs-as well as two early-branching S100 proteins found in the tunicate Oikopleura dioica-bind these metals with μM affinity and stoichiometries ranging from 1:1 to 3:1 (metal:protein). While binding is consistent across the tree, structural responses to binding are quite variable. Further, mutational analysis and structural modeling revealed that transition metal binding occurs at different sites in different S100 proteins. This is consistent with multiple origins of transition metal binding over the evolution of this protein family. Our work reveals an evolutionary pattern in which the overall phenotype of binding is a constant feature of S100 proteins, even while the site and mechanism of binding is evolutionarily labile.
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.