ArticleNature2010
The structural basis for membrane binding and pore formation by lymphocyte perforin.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers.
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Who cites it
212 citing papers in PubMed, 400 citations in OpenAlex.
- Anchoring of perforin-2 via the transmembrane domain is required for antigen escape into the cytosol.The EMBO journal · 2026Article
- Pharmacological inhibition of perforin dampens CD8Diabetologia · 2026Article
- Molecular mechanism of pore formation by Plasmodium Perforin-like Protein 2.Nature communications · 2026Article
- Switchable Enzyme-Regulated ECM-Integrin-Cholesterol Signaling Orchestrate PD-L1 Dual Destabilization for Boosting Photo-Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Deciphering Membrane Pore Formation Mechanisms of Plasmodium falciparum Perforin-Like Protein 1 (PfPLP1).The Journal of membrane biology · 2026Article
- What Is the Role of Giant Endosomal Sorting Complexes Required for Transport (ESCRT) Structures in T Cell Activation?Advanced biology · 2026Article
- Maternal opioid use is associated with altered placental bacterial DNA and activation of immune-apoptotic pathways.NeuroImmune pharmacology and therapeutics · 2025Article
- Disrupting membranes, controlling cell fate: the role of pore-forming proteins in cell death and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Expression and localization of lysosomal-associated membrane protein 1- and perforin-based hybrid molecules in the murine cytotoxic T cell line CTLL-2.Cytotechnology · 2025Article
- Updates in the pathogenesis of SJS/TEN.Allergology international : official journal of the Japanese Society of Allergology · 2025Review
- Investigating neutrophil responses to stimuli: Comparative analysis of reactive species-dependent and independent mechanisms.Redox biology · 2025Article
- Molecular Subtyping and Therapeutic Targeting of IFNG-Driven Immunogenic Cell Death in Lung Adenocarcinoma.Cancer medicine · 2025Article
- Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.The Journal of clinical investigation · 2025Article
- Leveraging T cells for cancer immunotherapy.Immunity & inflammation · 2025Review
- Comprehensive evaluation of immune dysregulation in secondary hemophagocytic lymphohistiocytosis.Virulence · 2024Article
- Natural Killer cells at the frontline in the fight against cancer.Cell death & disease · 2024Review
- Perforin 1 in Cancer: Mechanisms, Therapy, and Outlook.Biomolecules · 2024Review
- Evidence of membranolytic targeting and intracellular citrullination in neutrophils isolated from patients with rheumatoid arthritis.Scientific reports · 2024Article
- Peripheral Blood CD8International journal of molecular sciences · 2024Article
- Cell softness renders cytotoxic T lymphocytes and T leukemic cells resistant to perforin-mediated killing.Nature communications · 2024Article
152 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell. The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis (type 2 FHL). Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin 'key-shaped' molecule, comprising an amino-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain followed by an epidermal growth factor (EGF) domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca(2+)-dependent membrane binding. Most unexpectedly, however, electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.
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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.