ArticleNature structural & molecular biology2024
Structural basis of the human NAIP/NLRC4 inflammasome assembly and pathogen sensing.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- The Co-Evolutionary Arms Race BetweenMicroorganisms · 2026Review
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Plant NLRs are getting into higher-order architectures.The Plant journal : for cell and molecular 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
- Discovery of potent and selective inhibitors of human NLRP3 with a novel mechanism of action.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
- Activation and regulation of NAIP/NLRC4 and NLRP3 inflammasomes during Salmonella infection: mechanisms and therapeutic implications.Molecular biology reports · 2025Review
- Review
- Silkworm Enzyme Hydrolysates Improve Memory in MCI Models via CREB-BDNF Signaling and Enhanced Brain Mitochondrial Function.Nutrients · 2025Article
- Review
- Signalling by co-operative higher-order assembly formation: linking evidence at molecular and cellular levels.The Biochemical journal · 2025Review
- Article
- Mechanisms conferring multi-layered protection against intestinal Salmonella Typhimurium infection.FEMS microbiology reviews · 2025Review
- Article
- NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study.BMC pediatrics · 2024Article
- Inflammasome activity regulation by PUFA metabolites.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NLR family caspase activation and recruitment domain-containing 4 (NLRC4) inflammasome is a critical cytosolic innate immune machine formed upon the direct sensing of bacterial infection and in response to cell stress during sterile chronic inflammation. Despite its major role in instigating the subsequent host immune response, a more complete understanding of the molecular events in the formation of the NLRC4 inflammasome in humans is lacking. Here we identify Bacillus thailandensis type III secretion system needle protein (Needle) as a potent trigger of the human NLR family apoptosis inhibitory protein (NAIP)/NLRC4 inflammasome complex formation and determine its structural features by cryogenic electron microscopy. We also provide a detailed understanding of how type III secretion system pathogen components are sensed by human NAIP to form a cascade of NLRC4 protomer through a critical lasso-like motif, a 'lock-key' activation model and large structural rearrangement, ultimately forming the full human NLRC4 inflammasome. These results shed light on key regulatory mechanisms specific to the NLRC4 inflammasome assembly, and the innate immune modalities of pathogen sensing in humans.
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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.