| First Author | Hu Z | Year | 2013 |
| Journal | Science | Volume | 341 |
| Issue | 6142 | Pages | 172-5 |
| PubMed ID | 23765277 | Mgi Jnum | J:245334 |
| Mgi Id | MGI:5917987 | Doi | 10.1126/science.1236381 |
| Citation | Hu Z, et al. (2013) Crystal structure of NLRC4 reveals its autoinhibition mechanism. Science 341(6142):172-5 |
| abstractText | Nucleotide-binding and oligomerization domain-like receptor (NLR) proteins oligomerize into multiprotein complexes termed inflammasomes when activated. Their autoinhibition mechanism remains poorly defined. Here, we report the crystal structure of mouse NLRC4 in a closed form. The adenosine diphosphate-mediated interaction between the central nucleotide-binding domain (NBD) and the winged-helix domain (WHD) was critical for stabilizing the closed conformation of NLRC4. The helical domain HD2 repressively contacted a conserved and functionally important alpha-helix of the NBD. The C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. Disruption of ADP-mediated NBD-WHD or NBD-HD2/NBD-LRR interactions resulted in constitutive activation of NLRC4. Together, our data reveal the NBD-organized cooperative autoinhibition mechanism of NLRC4 and provide insight into its activation. |
