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

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

Abstract: 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.

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.

Published online 16 June 2005

Include this information when citing this paper.

^* To whom correspondence should be addressed. E-mail: wilson{at}scripps.edu

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