title: Crystal structure of the Nod1 caspase activation and recruitment domain.
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.
authors.affiliation: Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Coussens
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Mowers
authors.forename: Christine
authors.initials: C
authors.lastname: McDonald
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nuñez
authors.forename: S
authors.initials: S
authors.lastname: Ramaswamy
mesh_terms: D001665:Binding Sites; D020169:Caspases / Q000737:chemistry* / Q000648:ultrastructure*; D003461:Crystallography; D004789:Enzyme Activation; D007930:Leucine / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D053474:Nod1 Signaling Adaptor Protein / Q000737:chemistry* / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D020169:Caspases; D007930:Leucine