Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

Clarissa Eibl, Manuel Hessenberger, Julia Wenger, Hans Brandstetter

Research output: Journal article (peer-reviewed)Journal article

19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2007-2018
Number of pages12
JournalActa Crystallographica Section D: Structural Biology
Issue number7
Publication statusPublished - Jul 2014
Externally publishedYes


  • Amino Acid Sequence
  • Chromatography, Gel
  • Circular Dichroism
  • Cytoskeletal Proteins/chemistry
  • Humans
  • Molecular Sequence Data
  • Nucleoside-Triphosphatase/chemistry
  • Protein Conformation
  • Pyrin
  • Sequence Homology, Amino Acid
  • NLRP14
  • pyrin domain

ASJC Scopus subject areas

  • Structural Biology


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