Yang, XinruYang, FanWang, WeiguangLin, GuangzhongHu, ZehanHan, ZhifuQi, YijunZhang, LimanWang, JiaweiSui, Sen-FangChai, Jijie2018-02-262017Yang, X., F. Yang, W. Wang, G. Lin, Z. Hu, Z. Han, Y. Qi, et al. 2017. “Structural basis for specific flagellin recognition by the NLR protein NAIP5.” Cell Research 28 (1): 35-47. doi:10.1038/cr.2017.148. http://dx.doi.org/10.1038/cr.2017.148.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868833The 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.en-USflagellinNAIP5NLRC4cryo-EMJournal Article2018-02-2610.1038/cr.2017.148