PDBsum entry 4n1k

Signaling protein

PDB id: 4n1k

Contents

Protein chains

88 a.a.

94 a.a.

Waters ×13

References listed in PDB file

Key reference

• Title: Structures of the nlrp14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions.
• Authors: C.Eibl, M.Hessenberger, J.Wenger, H.Brandstetter.
• Ref.: Acta Crystallogr D Biol Crystallogr, 2014, 70, 2007-2018. [DOI no: 10.1107/S1399004714010311]
• PubMed id: 25004977

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.