ArticleProceedings of the National Academy of Sciences of the United States of America2013
Visualization of pinholin lesions in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Designing the Next Generation of Endolysins: A Triple Strategy Integrating Bioinformatics Mining, Engineering Modification and Encapsulation Formulation.Probiotics and antimicrobial proteins · 2026Review
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- The short cytoplasmic region of phage T4 holin is essential for the transition from impermeable membrane protein complexes to permeable pores.Frontiers in microbiology · 2025Article
- Identifying components of theJournal of bacteriology · 2024Article
- Molecular Machinery of the Triad Holin, Endolysin, and Spanin: Key Players Orchestrating Bacteriophage-Induced Cell Lysis and their Therapeutic Applications.Protein and peptide letters · 2024Review
- Length matters: Functional flip of the short TatA transmembrane helix.Biophysical journal · 2023Article
- Endolysin Regulation in Phage Mu Lysis.mBio · 2022Article
- Bacteriophage-encoded lethal membrane disruptors: Advances in understanding and potential applications.Frontiers in microbiology · 2022Review
- Article
- Pinholin SBiochimica et biophysica acta. Biomembranes · 2021Article
- Antimicrobial Peptides: An Update on Classifications and Databases.International journal of molecular sciences · 2021Review
- Article
- The Phage T4 Antiholin RI Has a Cleavable Signal Peptide, Not a SAR Domain.Frontiers in microbiology · 2021Article
- Conformational Differences Are Observed for the Active and Inactive Forms of Pinholin SThe journal of physical chemistry. B · 2020Article
- Structural and functional characterization of the pore-forming domain of pinholin SProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Environmental Triggers ofFrontiers in microbiology · 2020Article
- Phage Lysis: Multiple Genes for Multiple Barriers.Advances in virus research · 2019Review
- Phage-Antibiotic Synergy via Delayed Lysis.Applied and environmental microbiology · 2018Article
- Enzymes and Mechanisms Employed by Tailed Bacteriophages to Breach the Bacterial Cell Barriers.Viruses · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Lambdoid phage 21 uses a pinholin-signal anchor release endolysin strategy to effect temporally regulated host lysis. In this strategy, the pinholin S(21)68 accumulates harmlessly in the bilayer until suddenly triggering to form lethal membrane lesions, consisting of S(21)68 heptamers with central pores <2 nm in diameter. The membrane depolarization caused by these pores activates the muralytic endolysin, R(21), leading immediately to peptidoglycan degradation. The lethal S(21)68 complexes have been designated as pinholes to distinguish from the micrometer-scale holes formed by canonical holins. Here, we used GFP fusions of WT and mutant forms of S(21)68 to show that the holin accumulates uniformly throughout the membrane until the time of triggering, when it suddenly redistributes into numerous small foci (rafts). Raft formation correlates with the depletion of the proton motive force, which is indicated by the potential-sensitive dye bis-(1,3-dibutylbarbituric acid)pentamethine oxonol. By contrast, GFP fusions of either antiholin variant irsS(21)68, which only forms inactive dimers, or nonlethal mutant S(21)68(S44C), which is blocked at an activated dimer stage of the pinhole formation pathway, were both blocked in a state of uniform distribution. In addition, fluorescence recovery after photobleaching revealed that, although the antiholin irsS(21)68-GFP fusion was highly mobile in the membrane (even when the proton motive force was depleted), more than one-half of the S(21)68-GFP molecules were immobile, and the rest were in mobile states with a much lower diffusion rate than the rate of irsS(21)68-GFP. These results suggest a model in which, after transiting into an oligomeric state, S(21)68 migrates into rafts with heterogeneous sizes, within which the final pinholes form.
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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.