ArticlePloS one2012
High fidelity processing and activation of the human α-defensin HNP1 precursor by neutrophil elastase and proteinase 3.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Mechanistic Insights into Human Defensin Antimicrobial Activity from Membrane Simulations.The Journal of membrane biology · 2026Article
- HNP-1: From Structure to Application Thanks to Multifaceted Functions.Microorganisms · 2025Review
- Self-Control of Inflammation during Tail Regeneration of Lizards.Journal of developmental biology · 2021Review
- Defensins: A Double-Edged Sword in Host Immunity.Frontiers in immunology · 2020Review
- Article
- Newborn sex-specific transcriptome signatures and gestational exposure to fine particles: findings from the ENVIRONAGE birth cohort.Environmental health : a global access science source · 2017Article
- Rhesus macaque θ-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-κB and MAPK pathways.Journal of leukocyte biology · 2015Article
- Article
- Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses.The Journal of clinical investigation · 2014Article
- Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis.Orphanet journal of rare diseases · 2014Article
- Antimicrobial peptides in reptiles.Pharmaceuticals (Basel, Switzerland) · 2014Article
- Article
- To fuse or not to fuse: what is your purpose?Protein science : a publication of the Protein Society · 2013Review
- Rattusin, an intestinal α-defensin-related peptide in rats with a unique cysteine spacing pattern and salt-insensitive antibacterial activities.Antimicrobial agents and chemotherapy · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The azurophilic granules of human neutrophils contain four α-defensins called human neutrophil peptides (HNPs 1-4). HNPs are tridisulfide-linked antimicrobial peptides involved in the intracellular killing of organisms phagocytosed by neutrophils. The peptides are produced as inactive precursors (proHNPs) which are processed to active microbicides by as yet unidentified convertases. ProHNP1 was expressed in E. coli and the affinity-purified propeptide isolated as two species, one containing mature HNP1 sequence with native disulfide linkages ("folded proHNP1") and the other containing non-native disulfide linked proHNP1 conformers (misfolded proHNP1). Native HNP1, liberated by CNBr treatment of folded proHNP1, was microbicidal against Staphylococcus aureus, but the peptide derived from misfolded proHNP1 was inactive. We hypothesized that neutrophil elastase (NE), proteinase 3 (PR3) or cathepsin G (CG), serine proteases that co-localize with HNPs in azurophil granules, are proHNP1 activating convertases. Folded proHNP1 was converted to mature HNP1 by both NE and PR3, but CG generated an HNP1 variant with an N-terminal dipeptide extension. NE and PR3 cleaved folded proHNP1 to produce a peptide indistinguishable from native HNP1 purified from neutrophils, and the microbicidal activities of in vitro derived and natural HNP1 peptides were equivalent. In contrast, misfolded proHNP1 conformers were degraded extensively under the same conditions. Thus, NE and PR3 possess proHNP1 convertase activity that requires the presence of the native HNP1 disulfide motif for high fidelity activation of the precursor in vitro.
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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.