Journal
IUBMB LIFE
Volume 65, Issue 10, Pages 851-862Publisher
WILEY
DOI: 10.1002/iub.1210
Keywords
NLR; NLRP; NACHT domain; nucleotide-binding; STAND ATPase
Categories
Funding
- University of Calgary URGC Seed Grant
Ask authors/readers for more resources
Nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) regulate innate immunity by activating inflammatory responses in a variety of biological systems following the recognition of pathogen- or disease-associated molecular patterns. NLRs are characterized by a central nucleotide-binding and oligomerization (NACHT) domain found in P-loop NTPases. In this review, we detail the functional and structural properties of the NACHT domain of a subfamily of NLRs, the NLRPs (NLR containing a pyrin domain), based on previous studies, sequence analysis, homology modeling, and structure predictions. Several NLRPs have been found to regulate inflammatory responses through the assembly of oligomeric caspase 1-activating platforms known as inflammasomes, the 3-dimensional structure of the NLRP NACHT domain has still not been solved. Homology modeling suggests that sequence variability within the NACHT domains of different NLRP family members may alter the topology of the ATP-binding pocket. Based on this finding, we discuss the potential therapeutic prospects aligned with the NACHT domain and the development of selective inhibitors of inflammasome activity. (c) 2013 IUBMB Life, 65(10):851-862, 2013
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available