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

By Jessica K. Bell, Istvan Botos, Pamela R. Hall, Janine Askins, Joseph Shiloach, David M. Segal and David R. Davies

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-Å 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 β-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

Topics: Biological Sciences
Publisher: National Academy of Sciences
Year: 2005
DOI identifier: 10.1073/pnas.0505077102
OAI identifier: oai:pubmedcentral.nih.gov:1182468
Provided by: PubMed Central
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