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Details on Person Intracellular bacterial lipopolysaccharide (LPS) binds to th...
| Class:Id | Summation:9953138 |
|---|---|
| _displayName | Intracellular bacterial lipopolysaccharide (LPS) binds to th... |
| _timestamp | 2025-08-14 15:54:22 |
| created | [InstanceEdit:9953148] Shamovsky, Veronica, 2025-05-28 |
| literatureReference | [LiteratureReference:9647669] Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death [LiteratureReference:9647649] Inflammatory Caspases: Activation and Cleavage of Gasdermin-D In Vitro and During Pyroptosis [LiteratureReference:9652838] Inflammatory caspases are innate immune receptors for intracellular LPS [LiteratureReference:9958643] Caspase-5: Structure, Pro-Inflammatory Activity and Evolution [LiteratureReference:9686131] Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes [LiteratureReference:9958631] The tetrapeptide sequence of IL-18 and IL-1β regulates their recruitment and activation by inflammatory caspases [LiteratureReference:9947798] High-affinity caspase-4 binding to LPS presented as high molecular mass aggregates or in outer membrane vesicles [LiteratureReference:9947828] Membrane vesicles from Pseudomonas aeruginosa activate the noncanonical inflammasome through caspase-5 in human monocytes [LiteratureReference:9947825] Detecting lipopolysaccharide in the cytosol of mammalian cells: Lessons from MD-2/TLR4 [LiteratureReference:9947805] The Role of Lipopolysaccharide-Induced Cell Signalling in Chronic Inflammation [LiteratureReference:9947800] Caspase-4 disaggregates lipopolysaccharide micelles via LPS-CARD interaction [LiteratureReference:9716215] Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling [LiteratureReference:9647685] Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores [LiteratureReference:9647674] Pore-forming activity and structural autoinhibition of the gasdermin family [LiteratureReference:9647662] GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death [LiteratureReference:9963522] GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes [LiteratureReference:9958663] Inflammatory caspase substrate specificities |
| modified | [InstanceEdit:9958687] Shamovsky, Veronica, 2025-06-24 [InstanceEdit:9958782] Shamovsky, Veronica, 2025-06-25 [InstanceEdit:9963552] Shamovsky, Veronica, 2025-08-14 [InstanceEdit:9963583] Shamovsky, Veronica, 2025-08-14 |
| text | Intracellular bacterial lipopolysaccharide (LPS) binds to the N-terminal caspase activation and recruitment domain (CARD) of caspase-5 (CASP5) (Shi J et al., 2014; Bitto NJ et al., 2018; reviewed by Eckhart L & Fischer H 2024). Upon LPS binding, CASP5 oligomerizes and undergoes activation via auto-proteolytic cleavage (Shi J et al., 2014; Viganò E et al., 2015). Activated CASP5 subsequently cleaves gasdermin D (GSDMD), a substrate also targeted by CASP1, CASP4, and Casp11, a murine homolog of human CASP4 and CASP5 (Shi J et al., 2014, 2015; Kayagaki N et al., 2015; Zhao Y et al., 2018; Wang K et al., 2020). The resulting N-terminal fragment of GSDMD oligomerizes to form pores in the cell membrane, leading to pyroptosis, a lytic, pro-inflammatory form of cell death that eliminates infected cells and prevents pathogen spread in mammals (Liu X et al., 2016; Ding J et al., 2016; Sborgi L et al., 2016; Aglietti RA et al., 2016). Similar to CASP4, CASP5 efficiently cleaves pro-interleukin-18 (pro-IL-18) at aspartic acid residue D36 to generate its mature, biologically active form (Shi X et al., 2023; Devant P et al., 2023; Exconde PM et al., 2023; reviewed by Exconde PM, 2024). In contrast, CASP5- and CASP4-mediated cleavage of pro-IL-1β at D27 yields an inactive fragment that lacks receptor-stimulating activity (Exconde PM et al., 2023; reviewed by Exconde PM, 2024). LPS can enter the host cell cytosol through several mechanisms, including endocytosis of LPS-containing outer membrane vesicles (OMVs), which are naturally secreted by Gram-negative bacteria (Wacker MA et al., 2017; Bitto NJ et al., 2018; reviewed by Barker JH & Weiss JP 2019; Page MJ et al., 2022;). Additionally, LPS may be released from phagocytosed bacteria following the rupture of phagolysosomal compartments and the fragmentation of bacterial membranes within the host cytosol. Due to its amphiphilic nature, LPS can self-assemble into micellar structures, with hydrophobic lipid A moieties clustered internally. These intracellular LPS species are recognized by CASP4 and likely by CASP5 (Wacker MA et al., 2017; An J et al., 2019). |
| (summation) | [Reaction:9686100] CASP5 binds LPS micelles [Homo sapiens] |
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