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

Science, 22 July 2005
Vol. 309, Issue 5734, p. 581-585
DOI: 10.1126/science.1115253

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

  1. Jungwoo Choe,
  2. Matthew S. Kelker,
  3. Ian A. Wilson*
  1. Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
  1. * To whom correspondence should be addressed. E-mail: wilson{at}
  • Published online 16 June 2005

  • Include this information when citing this paper.


Toll-like receptors (TLRs) play key roles in activating immune responses during infection. The human TLR3 ectodomain structure at 2.1 angstroms reveals a large horseshoe-shaped solenoid assembled from 23 leucine-rich repeats (LRRs). Asparagines conserved in the 24-residue LRR motif contribute extensive hydrogen-bonding networks for solenoid stabilization. TLR3 is largely masked by carbohydrate, but one face is glycosylation-free, which 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 double-stranded RNA.

    • Received for publication 24 May 2005.
    • Accepted for publication 8 June 2005.


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