Unknown

Dataset Information

0

The molecular structure of the Toll-like receptor 3 ligand-binding domain.


ABSTRACT: Innate immunity is the first line of defense against invading pathogens. Toll-like receptors (TLRs) act as sentinels of the innate immune system, sensing a variety of ligands from lipopolysaccharide to flagellin to dsRNA through their ligand-binding domain that is composed of leucine-rich repeats (LRRs). Ligand binding initiates a signaling cascade that leads to the up-regulation of inflammation mediators. In this study, we have expressed and crystallized the ectodomain (ECD) of human TLR3, which recognizes dsRNA, a molecular signature of viruses, and have determined the molecular structure to 2.4-A resolution. The overall horseshoe-shaped structure of the TLR3-ECD is formed by 23 repeating LRRs that are capped at each end by specialized non-LRR domains. The extensive beta-sheet on the molecule's concave surface forms a platform for several modifications, including insertions in the LRRs and 11 N-linked glycans. The TLR3-ECD structure indicates how LRR loops can establish distinct pathogen recognition receptors.

SUBMITTER: Bell JK 

PROVIDER: S-EPMC1182468 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

The molecular structure of the Toll-like receptor 3 ligand-binding domain.

Bell Jessica K JK   Botos Istvan I   Hall Pamela R PR   Askins Janine J   Shiloach Joseph J   Segal David M DM   Davies David R DR  

Proceedings of the National Academy of Sciences of the United States of America 20050725 31


Innate immunity is the first line of defense against invading pathogens. Toll-like receptors (TLRs) act as sentinels of the innate immune system, sensing a variety of ligands from lipopolysaccharide to flagellin to dsRNA through their ligand-binding domain that is composed of leucine-rich repeats (LRRs). Ligand binding initiates a signaling cascade that leads to the up-regulation of inflammation mediators. In this study, we have expressed and crystallized the ectodomain (ECD) of human TLR3, whic  ...[more]

Similar Datasets

2018-10-26 | PXD005575 | Pride
| S-EPMC5303882 | biostudies-literature
| S-EPMC5100906 | biostudies-literature
| S-EPMC7867599 | biostudies-literature
| S-EPMC10758278 | biostudies-literature
| S-EPMC2873197 | biostudies-literature
| S-EPMC193567 | biostudies-literature
| S-EPMC2635866 | biostudies-literature
| S-EPMC3434514 | biostudies-literature
| S-EPMC4821253 | biostudies-literature