ArticleThe Journal of biological chemistry2015
Structural Basis for Ca2+-mediated Interaction of the Perforin C2 Domain with Lipid Membranes.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- A Trichomonas vaginalis C2-XYPPX-repeat protein with a structured C2 domain displaying dampened flexibility upon binding calcium.Biochimie · 2026Article
- 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
- Human Vγ9Vδ2 T cells exhibit antifungal activity againstMicrobiology spectrum · 2024Article
- The Dysferlin C2A Domain Binds PI(4,5)P2 and Penetrates Membranes.Journal of molecular biology · 2023Article
- Case report: Ruxolitinib plus dexamethasone as first-line therapy in haemophagocytic lymphohistiocytosis.Frontiers in oncology · 2023Article
- Surface plasmon resonance and microscale thermophoresis approaches for determining the affinity of perforin for calcium ions.Frontiers in immunology · 2023Article
- Lipid specificity of the immune effector perforin.Faraday discussions · 2021Article
- Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy.Communications biology · 2021Article
- The C2 domain of calpain 5 contributes to enzyme activation and membrane localization.Biochimica et biophysica acta. Molecular cell research · 2021Article
- Knocking 'em Dead: Pore-Forming Proteins in Immune Defense.Annual review of immunology · 2020Review
- Ancient but Not Forgotten: New Insights Into MPEG1, a Macrophage Perforin-Like Immune Effector.Frontiers in immunology · 2020Review
- Perforin proteostasis is regulated through its C2 domain: supra-physiological cell death mediated by T431D-perforin.Cell death and differentiation · 2018Article
- Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands.The EMBO journal · 2017Article
- Antigen-specific CD8Nature communications · 2017Article
- Benzenesulphonamide inhibitors of the cytolytic protein perforin.Bioorganic & medicinal chemistry letters · 2017Article
- IL-2 augments the therapeutic efficacy of adoptively transferred B cells which directly kill tumor cells via the CXCR4/CXCL12 and perforin pathways.Oncotarget · 2016Article
- The Effects of Ca2+ Concentration and E200K Mutation on the Aggregation Propensity of PrPC: A Computational Study.PloS one · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer cells and cytotoxic T-lymphocytes deploy perforin and granzymes to kill infected host cells. Perforin, secreted by immune cells, binds target membranes to form pores that deliver pro-apoptotic granzymes into the target cell. A crucial first step in this process is interaction of its C2 domain with target cell membranes, which is a calcium-dependent event. Some aspects of this process are understood, but many molecular details remain unclear. To address this, we investigated the mechanism of Ca(2+) and lipid binding to the C2 domain by NMR spectroscopy and x-ray crystallography. Calcium titrations, together with dodecylphosphocholine micelle experiments, confirmed that multiple Ca(2+) ions bind within the calcium-binding regions, activating perforin with respect to membrane binding. We have also determined the affinities of several of these binding sites and have shown that this interaction causes a significant structural rearrangement in CBR1. Thus, it is proposed that Ca(2+) binding at the weakest affinity site triggers changes in the C2 domain that facilitate its interaction with lipid membranes.
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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.