4N1J

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

Summary for 4N1J

• Entry DOI: 10.2210/pdb4n1j/pdb
• Related: 4N1K 4N1L
• Descriptor: NACHT, LRR and PYD domains-containing protein 14, GLYCEROL (3 entities in total)
• Functional Keywords: death domain fold, pyrin domain, nod-like receptor, signaling protein, protein binding, spermatogenesis, innate immunity
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 50086.59

Authors

Eibl, C.,Hessenberger, M.,Wenger, J.,Brandstetter, H. (deposition date: 2013-10-04, release date: 2014-07-16, Last modification date: 2017-11-15)

Primary citation

Eibl, C.,Hessenberger, M.,Wenger, J.,Brandstetter, H.
Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions.
Acta Crystallogr.,Sect.D, 70:2007-2018, 2014

PubMed Abstract: 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 α6, resulting in an extended α5/6 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.

PubMed: 25004977
DOI: 10.1107/S1399004714010311

Experimental method

X-RAY DIFFRACTION (2.6 Å)