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TitleStructural basis for specific flagellin recognition by the NLR protein NAIP5.
Journal, issue, pagesCell Res, Vol. 28, Issue 1, Page 35-47, Year 2018
Publish dateNov 28, 2017
AuthorsXinru Yang / Fan Yang / Weiguang Wang / Guangzhong Lin / Zehan Hu / Zhifu Han / Yijun Qi / Liman Zhang / Jiawei Wang / Sen-Fang Sui / Jijie Chai /
PubMed AbstractThe 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 ...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.
External linksCell Res / PubMed:29182158 / PubMed Central
MethodsEM (single particle)
Resolution4.28 Å
Structure data

EMDB-6845, PDB-5yud:
Flagellin derivative in complex with the NLR protein NAIP5
Method: EM (single particle) / Resolution: 4.28 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

Source
  • mus musculus (house mouse)
  • salmonella typhimurium (strain lt2 / sgsc1412 / atcc 700720) (bacteria)
KeywordsIMMUNE SYSTEM / Flagellin / NAIP5 / NLRC4 / Cryo-EM

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