4KXF

Crystal structure of NLRC4 reveals its autoinhibition mechanism

Summary for 4KXF

• Entry DOI: 10.2210/pdb4kxf/pdb
• Descriptor: NLR family CARD domain-containing protein 4, ADENOSINE-5'-DIPHOSPHATE, SULFATE ION (3 entities in total)
• Functional Keywords: auto-inhibition, muti-domain, innate immunity, phosphorylation, adp binding, immune system
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm, cytosol: Q3UP24
• Total number of polymer chains: 8
• Total formula weight: 939337.61

Authors

Chai, J.,Hu, Z. (deposition date: 2013-05-25, release date: 2013-07-24, Last modification date: 2024-11-13)

Primary citation

Hu, Z.,Yan, C.,Liu, P.,Huang, Z.,Ma, R.,Zhang, C.,Wang, R.,Zhang, Y.,Martinon, F.,Miao, D.,Deng, H.,Wang, J.,Chang, J.,Chai, J.
Crystal structure of NLRC4 reveals its autoinhibition mechanism
Science, 341:172-175, 2013

PubMed Abstract: 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 α-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.

PubMed: 23765277
DOI: 10.1126/science.1236381

Experimental method

X-RAY DIFFRACTION (3.2 Å)