SSRL | Highlights Archive | Headlines | Publications | User Resources | SLAC | Stanford University





Overall structure of human TLR3 ECD. (click on image for larger view)

 
Science Highlight
Wilson Lab

 




31 August 2005

  Structural Insights into Human Innate Immunity

Jungwoo Choe, Matthew S. Kelker and Ian A. Wilson, Department of Molecular Biology and The Skaggs Insitute for Chemical Biology, The Scripps Research Institute

 
 
 


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 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.