ArticleBiochemistry2016
Structural Features Essential to the Antimicrobial Functions of Human SPLUNC1.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- SPLUNC1/BPIFA1 Restrains Neutrophil-Dominant Inflammation and Coordinated Inflammatory Gene Programs During LPS-Induced Lung Injury.Biomolecules · 2026Article
- A lipid-binding protein in black-legged tick saliva selectively recognizesbioRxiv : the preprint server for biology · 2026Article
- Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.Human cell · 2026Review
- Is the SPLUNC1-Orai1 axis a critical determinant of lung health?Biochemical Society transactions · 2025Review
- UBR5 metabolically reprograms nasopharyngeal carcinoma cells to promote glycolysis and M2 polarization via SPLUNC1 signaling.NPJ precision oncology · 2024Article
- Airway Serous Cells: A Comparative Study of Spatial Distribution and Abundance among Species.Journal of respiratory biology and translational medicine · 2024Article
- Macrophage SPLUNC-ing Clears Bacteria in the Lung.American journal of respiratory and critical care medicine · 2024Article
- Lung SPLUNC1 Peptide Derivatives in the Lipid Membrane Headgroup Kill Gram-Negative Planktonic and Biofilm Bacteria.Biomacromolecules · 2023Article
- Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation.International journal of molecular sciences · 2023Article
- Biofilm Formation byInternational journal of molecular sciences · 2022Review
- Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.Biological reviews of the Cambridge Philosophical Society · 2022Review
- SPLUNC1 is a negative regulator of the Orai1 CaPhysiological reports · 2022Article
- BPIFA1 is a secreted biomarker of differentiating human airway epithelium.Frontiers in cellular and infection microbiology · 2022Article
- SPLUNC1: a novel marker of cystic fibrosis exacerbations.The European respiratory journal · 2021Article
- Acidic Microenvironment Determines Antibiotic Susceptibility and Biofilm Formation ofFrontiers in microbiology · 2021Article
- Degradation of bacterial permeability family member A1 (BPIFA1) by house dust mite (HDM) cysteine protease Der p 1 abrogates immune modulator function.International journal of biological macromolecules · 2020Article
- ENaC regulation by phospholipids and DGK explained through mathematical modeling.Scientific reports · 2020Article
- The SPLUNC1-βENaC complex prevents Burkholderia cenocepacia invasion in normal airway epithelia.Respiratory research · 2020Article
- A Rare Mutation in SPLUNC1 Affects Bacterial Adherence and Invasion in Meningococcal Disease.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
SPLUNC1 is an abundantly secreted innate immune protein in the mammalian respiratory tract that exerts bacteriostatic and antibiofilm effects, binds to lipopolysaccharide (LPS), and acts as a fluid-spreading surfactant. Here, we unravel the structural elements essential for the surfactant and antimicrobial functions of human SPLUNC1 (short palate lung nasal epithelial clone 1). A unique α-helix (α4) that extends from the body of SPLUNC1 is required for the bacteriostatic, surfactant, and LPS binding activities of this protein. Indeed, we find that mutation of just four leucine residues within this helical motif to alanine is sufficient to significantly inhibit the fluid spreading abilities of SPLUNC1, as well as its bacteriostatic actions against Gram-negative pathogens Burkholderia cenocepacia and Pseudomonas aeruginosa. Conformational flexibility in the body of SPLUNC1 is also involved in the bacteriostatic, surfactant, and LPS binding functions of the protein as revealed by disulfide mutants introduced into SPLUNC1. In addition, SPLUNC1 exerts antibiofilm effects against Gram-negative bacteria, although α4 is not involved in this activity. Interestingly, though, the introduction of surface electrostatic mutations away from α4 based on the unique dolphin SPLUNC1 sequence, and confirmed by crystal structure, is shown to impart antibiofilm activity against Staphylococcus aureus, the first SPLUNC1-dependent effect against a Gram-positive bacterium reported to date. Together, these data pinpoint SPLUNC1 structural motifs required for the antimicrobial and surfactant actions of this protective human protein.
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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.