| First Author | Yang X | Year | 2018 |
| Journal | Cell Res | Volume | 28 |
| Issue | 1 | Pages | 35-47 |
| PubMed ID | 29182158 | Mgi Jnum | J:257333 |
| Mgi Id | MGI:6120354 | Doi | 10.1038/cr.2017.148 |
| Citation | Yang X, et al. (2018) Structural basis for specific flagellin recognition by the NLR protein NAIP5. Cell Res 28(1):35-47 |
| abstractText | 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 A 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. |
