8fml
From Proteopedia
Cryo-EM structure of NLR family apoptosis inhibitory protein 5 (NAIP5) in complex with a full-length flagellin (FliC) ligand
Structural highlights
FunctionBIR1E_MOUSE Sensor component of the NLRC4 inflammasome that specifically recognizes and binds flagellin from pathogenic bacteria such as Legionella or Salmonella. Association of pathogenic bacteria proteins drives in turn drive assembly and activation of the NLRC4 inflammasome, promoting caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri. Prevents motor-neuron apoptosis induced by a variety of signals.[1] [2] Publication Abstract from PubMedThe NAIP (NLR family apoptosis inhibitory protein)/NLRC4 (NLR family CARD containing protein 4) inflammasome senses Gram-negative bacterial ligand. In the ligand-bound state, the winged helix domain of NAIP forms a steric clash with NLRC4 to open it up. However, how ligand binding activates NAIP is less clear. Here, we investigated the dynamics of the ligand-binding region of inactive NAIP5 and solved the cryo-EM structure of NAIP5 in complex with its specific ligand, FliC from flagellin, at 2.9-A resolution. The structure revealed a "trap and lock" mechanism in FliC recognition, whereby FliC-D0(C) is first trapped by the hydrophobic pocket of NAIP5, then locked in the binding site by ID (insertion domain) and C-terminal tail of NAIP5. The FliC-D0(N) domain further inserts into ID to stabilize the complex. According to this mechanism, FliC triggers the conformational change of NAIP5 by bringing multiple flexible domains together. Structural basis for flagellin-induced NAIP5 activation.,Paidimuddala B, Cao J, Zhang L Sci Adv. 2023 Dec 8;9(49):eadi8539. doi: 10.1126/sciadv.adi8539. Epub 2023 Dec 6. PMID:38055825[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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