ArticleNature structural & molecular biology2023
Mechanism of NAIP-NLRC4 inflammasome activation revealed by cryo-EM structure of unliganded NAIP5.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Pyroptosis: Molecular mechanisms and function.Journal of physiology and biochemistry · 2026Review
- The Co-Evolutionary Arms Race BetweenMicroorganisms · 2026Review
- TAK1 integrates the NLRP1 inflammasome into the innate immune response to double-stranded RNA.bioRxiv : the preprint server for biology · 2026Article
- Supramolecular Assemblies Drive Activation of Inflammasomes.Advances in experimental medicine and biology · 2026Review
- PANoptosis nexus in ischemia-reperfusion injury: from integrated cell death mechanisms to novel therapeutic opportunities.Frontiers in immunology · 2026Review
- Immunoregulatory mechanisms in parasitic eosinophilic lung disease: the role of IgE immune complexes and NLRC4 inflammasome.Frontiers in immunology · 2026Review
- Proton-activated chloride channel governs phagosome-mediated antibacterial immunity in peritoneal macrophages.The Journal of experimental medicine · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- New insights into the noncanonical inflammasome point to caspase-4 as a druggable target.Nature reviews. Immunology · 2025Review
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Phagosome-mediated anti-bacterial immunity is governed by the proton-activated chloride channel in peritoneal macrophages.bioRxiv : the preprint server for biology · 2025Article
- The changes of NLRs family members in the brain of AD mouse model and AD patients.Frontiers in immunology · 2025Article
- Inflammasome protein scaffolds the DNA damage complex during tumor development.Nature immunology · 2024Article
- Mechanistic insights from inflammasome structures.Nature reviews. Immunology · 2024Review
- Strategies of bacterial detection by inflammasomes.Cell chemical biology · 2024Review
- The interaction of inflammasomes and gut microbiota: novel therapeutic insights.Cell communication and signaling : CCS · 2024Review
- The role of inflammasomes in human diseases and their potential as therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Plant NLR immunity activation and execution: a biochemical perspective.Open biology · 2024Review
- Structural basis of the human NAIP/NLRC4 inflammasome assembly and pathogen sensing.Nature structural & molecular biology · 2024Article
- Structural basis for flagellin-induced NAIP5 activation.Science advances · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The nucleotide-binding domain (NBD), leucine rich repeat (LRR) domain containing protein family (NLR family) apoptosis inhibitory proteins (NAIPs) are cytosolic receptors that play critical roles in the host defense against bacterial infection. NAIPs interact with conserved bacterial ligands and activate the NLR family caspase recruitment domain containing protein 4 (NLRC4) to initiate the NAIP-NLRC4 inflammasome pathway. Here we found the process of NAIP activation is completely different from NLRC4. Our cryo-EM structure of unliganded mouse NAIP5 adopts an unprecedented wide-open conformation, with the nucleating surface fully exposed and accessible to recruit inactive NLRC4. Upon ligand binding, the winged helix domain (WHD) of NAIP5 undergoes roughly 20° rotation to form a steric clash with the inactive NLRC4, which triggers the conformational change of NLRC4 from inactive to active state. We also show the rotation of WHD places the 17-18 loop at a position that directly bind the active NLRC4 and stabilize the NAIP5-NLRC4 complex. Overall, these data provide structural mechanisms of inactive NAIP5, the process of NAIP5 activation and NAIP-dependent NLRC4 activation.
Indexed as
Identifiers
What OpenQuestion holds
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.