Abstract
The Caspase Recruitment Domain (CARD) from the innate immune receptor NOD1 was crystallized with Ubiquitin (Ub). NOD1 CARD was present as a helix-swapped homodimer similar to other structures of NOD1 CARD, and Ub monomers formed a homodimer similar in conformation to Lys48-linked di-Ub. The interaction between NOD1 CARD and Ub in the crystal was mediated by novel binding sites on each molecule. Comparisons of these sites to previously identified interaction surfaces on both molecules were made along with discussion of their potential functional significance.
Highlights
NOD1 is an innate immune receptor that recognizes c-Dglutamyl-meso-diaminopimelic acid, a dipeptide present in peptidoglycan of bacteria, and activates inflammation and autophagy in response to bacterial infection [1,2]
The asymmetric unit of the crystal structure contains one NOD1 Caspase Recruitment Domain (CARD) and one Ub, while symmetry-related molecules reveal that both NOD1 CARD and Ub form homodimers (Figure 1A)
Superposition of the NOD1 CARD dimer determined in this structure with those previously determined shows close similarity with RMSD values of 1.21 Aand 1.79 Aover the Ca chain for 2NSN [22] and 2NZ7 [21], respectively
Summary
NOD1 is an innate immune receptor that recognizes c-Dglutamyl-meso-diaminopimelic acid (iE-DAP), a dipeptide present in peptidoglycan of bacteria, and activates inflammation and autophagy in response to bacterial infection [1,2]. In addition to CARDs, the DD superfamily includes Death Domains, Death Effector Domains and Pyrin Domains These domains are typically around 100 amino acid residues in length and share a common six-helical bundle structural fold. They are involved in almost all aspects of immune and apoptotic signaling, and are found on various receptors, such as NOD1, as well as downstream signaling molecules such as RIP2, the effector kinase for NOD1 [11]. The majority of these domains have yet to be characterized structurally, and there are even fewer data describing how DDs complex with effector proteins. Ub has been found to bind the CARDs of the innate immune receptors NOD1, NOD2, RIG-1 and MDA5 and regulate their activity [12,13,14]
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