Innate immune sentinels: LRR_6 receptor scaffolds in pattern recognition
🧪 lmctl-orchestrated review — written by an orchestrated team of AI agents, grounded in 863 papers from lmmol's literature graph. Citations link to their source on PubMed.
| Protein | Papers |
|---|---|
| NACHT, LRR and PYD domains-containing protein 3 | 84 |
| Nucleotide-binding oligomerization domain-containing protein 2 | 62 |
| NACHT, LRR and PYD domains-containing protein 3 | 49 |
| Toll-like receptor 4 | 49 |
| NACHT, LRR and PYD domains-containing protein 1 | 48 |
| Ran GTPase-activating protein 1 | 35 |
| Nucleotide-binding oligomerization domain-containing protein 1 | 29 |
| Nucleotide-binding oligomerization domain-containing protein 2 | 28 |
Leucine-rich-repeat 6-domain proteins are recurring scaffolds that couple danger detection to inflammation with a shared architecture: modular sensing, adaptor recruitment, and controlled activation thresholds.
1. Core logic and architecture
The inflammasome remains the anchor model: receptor assembly becomes a caspase-activating platform and controls IL-1β processing [1]. In NOD and related families, homologous folds support common signaling logic even as downstream outcomes differ by context [2]. Early TLR work established that bacterial DNA sensing in innate cells also relies on this receptor-family architecture, with distinct ligand channels and immediate inflammatory output [3][4].
2. What changed in recent work
Recent results separated trigger-specific sensing from common activation nodes: inflammatory danger ligands and metabolic stress can both feed NLRP3 pathways through shared ionic and stress channels such as potassium perturbation [5][6][7]. Environmental activators and particulate stress then fit into the same gatekeeping model, reinforcing that context can dominate domain composition[8].
3. New reading posture in this family
The major shift for interpretation is to treat these families as control-dominant modules. ASC-dependent polymerization and adaptor geometry explain why similar receptor inputs can produce different outcomes and disease phenotypes [9][10]. Disease links such as Crohn’s-associated NOD2 variants remain central while recognizing that this is a network-level phenomenon, not a single-gene story [11][12][13].
4. Practical reading strategy on lmmol
Prioritize nodes where inflammasome and NOD/TLR modules cluster with shared evidence (for example NLRP3, NOD2, TLR4, ASC, NEK7) and then use recency-weighted co-citation to separate durable principles from transient findings[14]. Keep older landmarks as context and let newer domain-mechanics papers set direction.
- NOD2
- NLRP3
- TLR4
- ASC
- NLRP1
- NEK7
References
- Martinon F., Burns K., Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 2002. PubMed 4,982×
- Zhou R., Yazdi A.S., Menu P., Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011. PubMed 4,660×
- Hemmi H., Takeuchi O., Kawai T., Kaisho T. et al. A Toll-like receptor recognizes bacterial DNA. Nature 2000. PubMed 4,959×
- Medzhitov R., Preston-Hurlburt P., Janeway C.A. Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997. PubMed 3,931×
- Martinon F., Petrilli V., Mayor A., Tardivel A. et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006. PubMed 4,166×
- Mariathasan S., Weiss D.S., Newton K., McBride J. et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 2006. PubMed 2,501×
- He Y., Zeng M.Y., Yang D., Motro B. et al. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 2016. PubMed 1,081×
- Munoz-Planillo R., Kuffa P., Martinez-Colon G., Smith B.L. et al. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 2013. PubMed 1,789×
- Lu A., Magupalli V.G., Ruan J., Yin Q. et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 2014. PubMed 1,150×
- Hoffman H.M., Mueller J.L., Broide D.H., Wanderer A.A. et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat. Genet 2001. PubMed 1,312×
- Girardin S.E., Boneca I.G., Carneiro L.A., Antignac A. et al. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 2003. PubMed 1,198×
- Kobayashi K.S., Chamaillard M., Ogura Y., Henegariu O. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005. PubMed 1,364×
- Ogura Y., Inohara N., Benito A., Chen F.F. et al. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J. Biol. Chem 2001. PubMed 1,124×
- Arbour N.C., Lorenz E., Schutte B.C., Zabner J. et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet 2000. PubMed 1,582×