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Published Online June 16, 2005
Science DOI: 10.1126/science.1115253

Reports

Submitted on May 24, 2005
Accepted on June 9, 2005

Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain

Jungwoo Choe 1, Matthew S. Kelker 1, Ian A. Wilson 1*

1 Department of Molecular Biology and Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed.
Ian A. Wilson , E-mail: wilson{at}scripps.edu

Toll-like receptors (TLRs) play key roles in activating immune responses during infection. The human TLR3 ectodomain structure at 2.1 Å reveals a large horseshoe-shaped solenoid assembled from 23 leucine-rich repeats (LRRs). Asparagines conserved in the 24-mer LRR motif contribute extensive hydrogen-bonding networks for solenoid stabilization. TLR3 is largely masked by carbohydrate, but one face is glycosylation-free that suggests its potential role in ligand binding and oligomerization. Highly-conserved surface residues and a TLR3-specific LRR insertion form a homodimer interface in the crystal, whereas two patches of positively-charged residues and a second insertion would provide an appropriate binding site for dsRNA.


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