2MJM

The solution NMR structure of the NLRC5 caspase recruitment domain (CARD)

Summary for 2MJM

• Entry DOI: 10.2210/pdb2mjm/pdb
• NMR Information: BMRB: 19732
• Descriptor: Protein NLRC5 (1 entity in total)
• Functional Keywords: nlrc5, card, rig-i, protein binding, death fold, protein-protein interaction, inflammation, innate immune system, signaling protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm (By similarity): C3VPR6
• Total number of polymer chains: 1
• Total formula weight: 11669.41

Authors

Gutte, P.G.M.,Zerbe, O. (deposition date: 2014-01-12, release date: 2014-09-03, Last modification date: 2024-05-15)

Primary citation

Gutte, P.G.,Jurt, S.,Grutter, M.G.,Zerbe, O.
Unusual structural features revealed by the solution NMR structure of the NLRC5 caspase recruitment domain.
Biochemistry, 53:3106-3117, 2014

PubMed Abstract: The cytosolic nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) are key sensors for bacterial and viral invaders and endogenous stress signals. NLRs contain a varying N-terminal effector domain that regulates the downstream signaling events upon its activation and determines the subclass to which a NLR member belongs. NLRC5 contains an unclassified N-terminal effector domain that has been reported to interact downstream with the tandem caspase recruitment domain (CARD) of retinoic acid-inducible gene I (RIG-I). Here we report the solution structure of the N-terminal effector domain of NLRC5 and in vitro interaction experiments with the tandem CARD of RIG-I. The N-terminal effector domain of NLRC5 adopts a six α-helix bundle with a general death fold, though it displays specific structural features that are strikingly different from the CARD. Notably, α-helix 3 is replaced by an ordered loop, and α-helix 1 is devoid of the characteristic interruption. Detailed structural alignments between the N-terminal effector domains of NLRC5 with a representative of each death-fold subfamily showed that NLRC5 fits best to the CARD subfamily and can be called an atypical CARD. Due to the specific structural features, the atypical CARD also displays a different electrostatic surface. Because the shape and charge of the surface is crucial for the establishment of a homotypic CARD-CARD interaction, these specific structural features seem to have a significant effect on the interaction between the atypical CARD of NLRC5 and the tandem RIG-I CARD.

PubMed: 24815518
DOI: 10.1021/bi500177x

Experimental method

SOLUTION NMR