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Structural basis for specific flagellin recognition by the NLR protein NAIP5.

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Yang X, Yang F, Wang W, Lin G, Hu Z, Han Z, Qi Y, Zhang L, Wang J, Sui SF, Chai J
OpenAccess logo Cell Res 28 35-47 (2018)
Cited: 33 times
EuropePMC logo PMID: 29182158

Abstract

The nucleotide-binding domain- and leucine-rich repeat (LRR)-containing proteins (NLRs) function as intracellular immune receptors to detect the presence of pathogen- or host-derived signals. The mechanisms of how NLRs sense their ligands remain elusive. Here we report the structure of a bacterial flagellin derivative in complex with the NLR proteins NAIP5 and NLRC4 determined by cryo-electron microscopy at 4.28 Å resolution. The structure revealed that the flagellin derivative forms two parallel helices interacting with multiple domains including BIR1 and LRR of NAIP5. Binding to NAIP5 results in a nearly complete burial of the flagellin derivative, thus stabilizing the active conformation of NAIP5. The extreme C-terminal side of the flagellin is anchored to a sterically constrained binding pocket of NAIP5, which likely acts as a structural determinant for discrimination of different bacterial flagellins by NAIP5, a notion further supported by biochemical data. Taken together, our results shed light on the molecular mechanisms underlying NLR ligand perception.

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  8. Clostridioides difficile Flagellin Activates the Intracellular NLRC4 Inflammasome. Chebly H, Marvaud JC, Safa L, Elkak AK, Kobeissy PH, Kansau I, Larrazet C. Int J Mol Sci 23 12366 (2022)
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