ArticleThe Journal of biological chemistry2012
Functional determinants of human enteric α-defensin HD5: crucial role for hydrophobicity at dimer interface.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 75 citations in OpenAlex.
- Human alpha-defensin 5 stabilizes the enterovirus A71 capsid and blocks infection.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic Insights into Human Defensin Antimicrobial Activity from Membrane Simulations.The Journal of membrane biology · 2026Article
- Effects of Bile on PathogenicBiomolecules · 2025Article
- Mechanisms of AAV neutralization by human alpha-defensins.PLoS pathogens · 2025Article
- Shigella infection is facilitated by interaction of human enteric α-defensin 5 with colonic epithelial receptor P2Y11.Nature microbiology · 2025Article
- Review
- Alpha-defensin binding expands human adenovirus tropism.PLoS pathogens · 2024Article
- Mechanisms and regulation of defensins in host defense.Signal transduction and targeted therapy · 2023Review
- A Single Surface-Exposed Amino Acid Determines Differential Neutralization of AAV1 and AAV6 by Human Alpha-Defensins.Journal of virology · 2023Article
- Flagella-driven motility is a target of human Paneth cell defensin activity.PLoS pathogens · 2023Article
- Mouse α-Defensins: Structural and Functional Analysis of the 17 Cryptdin Isoforms Identified from a Single Jejunal Crypt.Infection and immunity · 2023Article
- Molecular dynamics simulations of human α-defensin 5 (HD5) crossing gram-negative bacterial membrane.PloS one · 2023Article
- Human defensin-inspired discovery of peptidomimetic antibiotics.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Evaluation of the Binding Mechanism of Human Defensin 5 in a Bacterial Membrane: A Simulation Study.International journal of molecular sciences · 2021Article
- The penetration of human defensin 5 (HD5) through bacterial outer membrane: simulation studies.Journal of molecular modeling · 2021Article
- Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn's Disease.Inflammatory bowel diseases · 2021Article
- Defensins: A Double-Edged Sword in Host Immunity.Frontiers in immunology · 2020Review
- Human Enteric Defensin 5 PromotesInfection and immunity · 2019Article
- Antimicrobial peptide ROAD-1 triggers phase change in local membrane environment to execute its activity.Journal of molecular modeling · 2019Article
- α-Defensin HD5 StabilizesPathogens & immunity · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Human α-defensins are cationic peptides that self-associate into dimers and higher-order oligomers. They bind protein toxins, such as anthrax lethal factor (LF), and kill bacteria, including Escherichia coli and Staphylococcus aureus, among other functions. There are six members of the human α-defensin family: four human neutrophil peptides, including HNP1, and two enteric human defensins, including HD5. We subjected HD5 to comprehensive alanine scanning mutagenesis. We then assayed LF binding by surface plasmon resonance, LF activity by enzyme kinetic inhibition, and antibacterial activity by the virtual colony count assay. Most mutations could be tolerated, resulting in activity comparable with that of wild type HD5. However, the L29A mutation decimated LF binding and bactericidal activity against Escherichia coli and Staphylococcus aureus. A series of unnatural aliphatic and aromatic substitutions at position 29, including aminobutyric acid (Abu) and norleucine (Nle) correlated hydrophobicity with HD5 function. The crystal structure of L29Abu-HD5 depicted decreased hydrophobic contacts at the dimer interface, whereas the Nle-29-HD5 crystal structure depicted a novel mode of dimerization with parallel β strands. The effect of mutating Leu(29) is similar to that of a C-terminal hydrophobic residue of HNP1, Trp(26). In addition, in order to further clarify the role of dimerization in HD5 function, an obligate monomer was generated by N-methylation of the Glu(21) residue, decreasing LF binding and antibacterial activity against S. aureus. These results further characterize the dimer interface of the α-defensins, revealing a crucial role of hydrophobicity-mediated dimerization.
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.