Part:BBa_K2976000

Toll-like receptor 1

Toll-like receptor 1 (TLR1) is a transmembrane glycoprotein that participates in the innate immune response to microbial agents. TLR1 could form active heterodimers with TLR2 when exposed to some pathogen-associated molecular pattern molecules (PAMPs), and the heterodimers recognize plenty of substances in lipoarabinomannan (LAM) biosynthesis with the help of CD14.

Usage

In 2019 CPU_CHINA project, TLR1 is expressed along with TLR2 and CD14 to form the TLR2:TLR1:CD14 cluster on the designer cell membrane. As a Mtb sensor, the complex could recognize the substances of Mtb and then stimulate the downstream signaling pathway. Then, activated NF-κB initiates transcription of the gene circuits to express other proteins in our project.

Usage and Biology

After being activated with Mtb, the activation cluster TLR2:TLR1:CD14 triggers NF-kappa-B signaling pathways via MYD88 and TRAF6. NF-κB proteins exist in the cytoplasm in an inactive form because of their association with the IκB proteins. IκB proteins mask the nuclear-localization sequences (NLSs) of NF-κB subunits and retain it in the cytoplasm. Activation of TLR2:TLR1:CD14 cluster cause the degradation of IκB proteins by proteasomes. Then, NF-κB subunits could pass through the nuclear pore complex (NPC) and cause the expression of an array of pro-inflammatory cytokines and chemokines. Similarly, NF-κB subunits can also bind the NF-κB induced promoter and initiate transcription of the downstream genes.

References

Barton, G. M., & Kagan, J. C. (2009). A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nature reviews. Immunology, 9(8), 535–542. https://doi.org/10.1038/nri2587

Blasius, A. L., & Beutler, B. (2010). Intracellular toll-like receptors. Immunity, 32(3), 305–315. https://doi.org/10.1016/j.immuni.2010.03.012

Kawai, T., & Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature immunology, 11(5), 373–384. https://doi.org/10.1038/ni.1863

Lester, S. N., & Li, K. (2014). Toll-like receptors in antiviral innate immunity. Journal of molecular biology, 426(6), 1246–1264. https://doi.org/10.1016/j.jmb.2013.11.024

Li, X., Jiang, S., & Tapping, R. I. (2010). Toll-like receptor signaling in cell proliferation and survival. Cytokine, 49(1), 1–9. https://doi.org/10.1016/j.cyto.2009.08.010 "

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]