Cryo-EM structures of Toll-like receptors in complex with UNC93B1
- 11 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 28 (2), 173-180
- https://doi.org/10.1038/s41594-020-00542-w
Abstract
Nucleic acid–sensing Toll-like receptors (TLRs) play a pivotal role in innate immunity by recognizing foreign DNA and RNA. Compartmentalization of these TLRs in the endosome limits their activation by self-derived nucleic acids and reduces the possibility of autoimmune reactions. Although chaperone Unc-93 homolog B1, TLR signaling regulator (UNC93B1) is indispensable for the trafficking of TLRs from the endoplasmic reticulum to the endosome, mechanisms of UNC93B1-mediated TLR regulation remain largely unknown. Here, we report two cryo-EM structures of human and mouse TLR3–UNC93B1 complexes and a human TLR7–UNC93B1 complex. UNC93B1 exhibits structural similarity to the major facilitator superfamily transporters. Both TLRs interact with the UNC93B1 amino-terminal six-helix bundle through their transmembrane and luminal juxtamembrane regions, but the complexes of TLR3 and TLR7 with UNC93B1 differ in their oligomerization state. The structural information provided here should aid in designing compounds to combat autoimmune diseases.Keywords
This publication has 40 references indexed in Scilit:
- Unc93B1 Restricts Systemic Lethal Inflammation by Orchestrating Toll-like Receptor 7 and 9 TraffickingImmunity, 2011
- Nucleic acid sensing Toll-like receptors in autoimmunityCurrent Opinion in Immunology, 2010
- Pattern Recognition Receptors and InflammationCell, 2010
- Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensingThe Journal of Experimental Medicine, 2009
- UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomesNature, 2008
- The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signalingThe Journal of cell biology, 2007
- The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9Nature Immunology, 2006
- Automated electron microscope tomography using robust prediction of specimen movementsJournal of Structural Biology, 2005
- Coot: model-building tools for molecular graphicsActa Crystallographica Section D-Biological Crystallography, 2004
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004