5AJ2

Cryo electron tomography of the Naip5-Nlrc4 inflammasome

Summary for 5AJ2

• Entry DOI: 10.2210/pdb5aj2/pdb
• EMDB information: 2901
• Descriptor: NLR FAMILY CARD DOMAIN-CONTAINING PROTEIN 4 (3 entities in total)
• Functional Keywords: apoptosis
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Cellular location: Cytoplasm, cytosol : Q3UP24 Q3UP24 Q3UP24
• Total number of polymer chains: 3
• Total formula weight: 117050.12

Authors

Diebolder, C.A.,Halff, E.F.,Koster, A.J.,Huizinga, E.G.,Koning, R.I. (deposition date: 2015-02-20, release date: 2015-11-11, Last modification date: 2024-05-08)

Primary citation

Diebolder, C.A.,Halff, E.F.,Koster, A.J.,Huizinga, E.G.,Koning, R.I.
Cryoelectron Tomography of the Naip5/Nlrc4 Inflammasome: Implications for Nlr Activation.
Structure, 23:2349-, 2015

PubMed Abstract: Inflammasomes are high molecular weight protein complexes that play a crucial role in innate immunity by activating caspase-1. Inflammasome formation is initiated when molecules originating from invading microorganisms activate nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) and induce NLR multimerization. Little is known about the conformational changes involved in NLR activation and the structural organization of NLR multimers. Here, we show by cryoelectron tomography that flagellin-induced NAIP5/NLRC4 multimers form right- and left-handed helical polymers with a diameter of 28 nm and a pitch of 6.5 nm. Subtomogram averaging produced an electron density map at 4 nm resolution, which was used for rigid body fitting of NLR subdomains derived from the crystal structure of dormant NLRC4. The resulting structural model of inflammasome-incorporated NLRC4 indicates that a prominent rotation of the LRR domain of NLRC4 is necessary for multimer formation, providing unprecedented insight into the conformational changes that accompany NLR activation.

PubMed: 26585513
DOI: 10.1016/J.STR.2015.10.001

Experimental method

ELECTRON MICROSCOPY (40 Å)