4n1j

Publication Abstract from PubMed

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.

Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions.,Eibl C, Hessenberger M, Wenger J, Brandstetter H Acta Crystallogr D Biol Crystallogr. 2014 Jul;70(Pt 7):2007-18. doi:, 10.1107/S1399004714010311. Epub 2014 Jun 29. PMID:25004977^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.