Crystal structure of the Nod1 caspase activation and recruitment domain

Biochem Biophys Res Commun. 2007 Feb 2;353(1):1-5. doi: 10.1016/j.bbrc.2006.11.122. Epub 2006 Dec 6.

Abstract

Nod-like receptors (NLRs), Nod1 and Nod2 are cytosolic detectors of pathogen-associated molecular patterns (PAMPs). Nod1 is a three-domain protein, consisting of a caspase activation and recruitment domain (CARD), a nucleotide-binding oligomerization domain (NOD), and a leucine-rich repeat domain (LRR). The binding of PAMPs to the LRR results in the activation of signaling through homophilic CARD-CARD interactions. Several CARD structures have been determined, including a recent NMR structure of Nod1 CARD. In contrast to the reported NMR structure, the crystal structure reported here is a dimer, where the sixth helix is swapped between two monomers. While the overall structure is very similar to the known CARD structures, this is the first report of a homodimeric CARD structure. The ability of the CARD to exist in monomeric and dimeric forms suggests another level of regulation in the activation of NLR proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Caspases / chemistry*
  • Caspases / ultrastructure*
  • Crystallography
  • Enzyme Activation
  • Leucine / chemistry*
  • Models, Chemical*
  • Models, Molecular*
  • Nod1 Signaling Adaptor Protein / chemistry*
  • Nod1 Signaling Adaptor Protein / ultrastructure*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary

Substances

  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • Caspases
  • Leucine