A molecular model of the full-length human NOD-like receptor family CARD domain containing 5 (NLRC5) protein
- Equal contributors
1 Department of Biochemistry and Molecular Biology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, POB 6, H-4012 Debrecen, Hungary
2 Department of Physiology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
BMC Bioinformatics 2013, 14:275 doi:10.1186/1471-2105-14-275Published: 17 September 2013
Pattern recognition receptors of the immune system have key roles in the regulation of pathways after the recognition of microbial- and danger-associated molecular patterns in vertebrates. Members of NOD-like receptor (NLR) family typically function intracellularly. The NOD-like receptor family CARD domain containing 5 (NLRC5) is the largest member of this family that also contains the largest number of leucine-rich repeats (LRRs).
Due to the lack of crystal structures of full-length NLRs, projects have been initiated with the aim to model certain or all members of the family, but systematic studies did not model the full-length NLRC5 due to its unique domain architecture.
Our aim was to analyze the LRR sequences of NLRC5 and some NLRC5-related proteins and to build a model for the full-length human NLRC5 by homology modeling.
LRR sequences of NLRC5 were aligned and were compared with the consensus pattern of ribonuclease inhibitor protein (RI)-like LRR subfamily. Two types of alternating consensus patterns previously identified for RI repeats were also found in NLRC5. A homology model for full-length human NLRC5 was prepared and, besides the closed conformation of monomeric NLRC5, a heptameric platform was also modeled for the opened conformational NLRC5 monomers.
Identification of consensus patterns of leucine-rich repeat sequences helped to identify LRRs in NLRC5 and to predict their number and position within the protein. In spite of the lack of fully adequate template structures, the presence of an untypical CARD domain and unusually high number of LRRs in NLRC5, we were able to construct a homology model for both the monomeric and homo-heptameric full-length human NLRC5 protein.