We have to defend ourselves from the challenge of microbial pathogens every day. Innate immune system represents the first line of defense against microorganisms by selectively detecting foreign molecules. The Toll-like receptors (TLRs) are one of the most important sensors of the innate immune system and recognize conserved molecules from various pathogens including viruses, bacteria, fungi and parasites. Using x-ray data collected at SSRL Beam Line 11-1 and at the ALS, scientists at The Scripps Research Institute have determined the 2.1 Å x-ray crystal structure of the ligand binding domain of one of the human TLRs (TLR-3). Human TLR3 is activated by double-stranded RNA associated with viral infection. The structure shows a large horseshoe-shaped "solenoid" assembled from 23 leucine-rich repeats (LRR). One side of the TLR3 is glycosylation-free and suggests its potential role in ligand binding and oligomerization. Two patches of positively charged residues and a TLR3-specific LRR insertion may provide an appropriate binding site for negatively-charged double-stranded RNA.