Structural basis for specific flagellin recognition by the NLR protein NAIP5

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2018,（1）
• 页码范围: 35-47
• 页数: 13页
• 语种: 英文
• DOI: 10.1038/cr.2017.148

摘要

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 NAIPS,a notion further supported by biochemical data.Taken together,our results shed light on the molecular mechanisms underlying NLR ligand perception.