4N1K: Crystal structures of NLRP14 pyrin domain reveal a conformational switch mechanism, regulating its molecular interactions

The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix alpha6, resulting in an extended alpha5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed.
PDB ID: 4N1KDownload
MMDB ID: 121503
PDB Deposition Date: 2013/10/4
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 4N1K: dimeric; determined by author and by software (PISA)
Molecular Components in 4N1K
Label Count Molecule
Proteins (2 molecules)
Nacht, LRR and PYD Domains-containing Protein 14(Gene symbol: NLRP14)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB