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.
Original language | English (US) |
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Pages (from-to) | 35-47 |
Number of pages | 13 |
Journal | Cell Research |
Volume | 28 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2018 |
Externally published | Yes |
Keywords
- NAIP5
- NLRC4
- cryo-EM
- flagellin
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology