8FML

Cryo-EM structure of NLR family apoptosis inhibitory protein 5 (NAIP5) in complex with a full-length flagellin (FliC) ligand

Summary for 8FML

• Entry DOI: 10.2210/pdb8fml/pdb
• EMDB information: 29296
• Descriptor: Baculoviral IAP repeat-containing protein 1e, Flagellin (2 entities in total)
• Functional Keywords: inflammasome, innate immunity, bacterial ligand, host-pathogen interaction, protein complex, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 213742.57

Authors

Paidimuddala, B.,Zhang, L. (deposition date: 2022-12-23, release date: 2024-01-10)

Primary citation

Paidimuddala, B.,Cao, J.,Zhang, L.
Structural basis for flagellin-induced NAIP5 activation.
Sci Adv, 9:eadi8539-eadi8539, 2023

PubMed Abstract: The NAIP (NLR family apoptosis inhibitory protein)/NLRC4 (NLR family CARD containing protein 4) inflammasome senses Gram-negative bacterial ligand. In the ligand-bound state, the winged helix domain of NAIP forms a steric clash with NLRC4 to open it up. However, how ligand binding activates NAIP is less clear. Here, we investigated the dynamics of the ligand-binding region of inactive NAIP5 and solved the cryo-EM structure of NAIP5 in complex with its specific ligand, FliC from flagellin, at 2.9-Å resolution. The structure revealed a "trap and lock" mechanism in FliC recognition, whereby FliC-D0 is first trapped by the hydrophobic pocket of NAIP5, then locked in the binding site by ID (insertion domain) and C-terminal tail of NAIP5. The FliC-D0 domain further inserts into ID to stabilize the complex. According to this mechanism, FliC triggers the conformational change of NAIP5 by bringing multiple flexible domains together.

PubMed: 38055825
DOI: 10.1126/sciadv.adi8539

Experimental method

ELECTRON MICROSCOPY (2.93 Å)