ArticleThe Journal of biological chemistry2011
Delineation of lipopolysaccharide (LPS)-binding sites on hemoglobin: from in silico predictions to biophysical characterization.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- One trigger, two fates: hemolysate shapes neutrophil extracellular traps (NETs) formation in a context-dependent manner.Frontiers in immunology · 2026Article
- Effects of Dietary Rumen-Protected Choline on Stress Alleviation, Antioxidant Modulation, and Haematological, Immunological, and Offspring Performance in Transitioning Goats.Veterinary medicine and science · 2025Article
- Klebsiella predominance in peripancreatic microbial spectrum is associated with the severity of infected pancreatic necrosis.BMC infectious diseases · 2025Article
- Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025Review
- Vitamin C-Dependent Uptake of Non-Heme Iron by Enterocytes, Its Impact on Erythropoiesis and Redox Capacity of Human Erythrocytes.Antioxidants (Basel, Switzerland) · 2024Review
- Erythrocytes of the common carp are immune sentinels that sense pathogen molecular patterns, engulf particles and secrete pro-inflammatory cytokines against bacterial infection.Frontiers in immunology · 2024Article
- Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle.eLife · 2023Article
- Various Facets of Pathogenic Lipids in Infectious Diseases: Exploring Virulent Lipid-Host Interactome and Their Druggability.The Journal of membrane biology · 2020Review
- The Anti-Microbial Peptide (Lin-SB056-1)Antibiotics (Basel, Switzerland) · 2020Article
- Bioinformatic Analysis of the Wound Peptidome Reveals Potential Biomarkers and Antimicrobial Peptides.Frontiers in immunology · 2020Article
- Proliferating tumor cells mimick glucose metabolism of mature human erythrocytes.Cell cycle (Georgetown, Tex.) · 2019Review
- Mechanisms of Hemolysis During Sepsis.Inflammation · 2018Review
- The Evolving Erythrocyte: Red Blood Cells as Modulators of Innate Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2018Review
- Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin.Cellular and molecular life sciences : CMLS · 2017Review
- Usefulness of ELISA Methods for Assessing LPS Interactions with Proteins and Peptides.PloS one · 2016Article
- Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae.Infection and immunity · 2016Article
- Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System.EBioMedicine · 2015Article
- Extracellular Hb enhances cardiac toxicity in endotoxemic guinea pigs: protective role of haptoglobin.Toxins · 2014Article
- A perspective on the role of extracellular hemoglobin on the innate immune system.DNA and cell biology · 2013Review
- Identification of hemopexin as an anti-inflammatory factor that inhibits synergy of hemoglobin with HMGB1 in sterile and infectious inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemoglobin (Hb) functions as a frontline defense molecule during infection by hemolytic microbes. Binding to LPS induces structural changes in cell-free Hb, which activates the redox activity of the protein for the generation of microbicidal free radicals. Although the interaction between Hb and LPS has implications for innate immune defense, the precise LPS-interaction sites on Hb remain unknown. Using surface plasmon resonance, we found that both the Hb α and β subunits possess high affinity LPS-binding sites, with K(D) in the nanomolar range. In silico analysis of Hb including phospho-group binding site prediction, structure-based sequence comparison, and docking to model the protein-ligand interactions showed that Hb possesses evolutionarily conserved surface cationic patches that could function as potential LPS-binding sites. Synthetic Hb peptides harboring predicted LPS-binding sites served to validate the computational predictions. Surface plasmon resonance analysis differentiated LPS-binding peptides from non-binders. Binding of the peptides to lipid A was further substantiated by a fluorescent probe displacement assay. The LPS-binding peptides effectively neutralized the endotoxicity of LPS in vitro. Additionally, peptide B59 spanning residues 59-95 of Hbβ attached to the surface of Gram-negative bacteria as shown by flow cytometry and visualized by immunogold-labeled scanning electron microscopy. Site-directed mutagenesis of the Hb subunits further confirmed the function of the predicted residues in binding to LPS. In summary, the integration of computational predictions and biophysical characterization has enabled delineation of multiple LPS-binding hot spots on the Hb molecule.
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