University of Tokyo researchers have elucidated how Toll-like receptor 9 (TLR9) binds to pathogen DNA, activating the innate immune system. This discovery is vital for the design of new antiviral, antibacterial, allergy and other drugs targeting TLR9.
Top row: Binding mode of TLR9 and a DNA sequence possessing a CpG motif. In the TLR dimer, one of the TLR9 molecules is colored green and one blue. The CpG motif has an elongated structure and attaches at two locations, one on each part of the TLR9 dimer, forming a 2:2 complex. Bottom row: Binding mode of TLR9 and antagonist DNA sequence. The inhibitor DNA forms a loop structure and binds on the interior of the horseshoe-shaped TLR9 ring, forming a 1:1 complex.
Credit:© 2015 Toshiyuki Shimizu.
Journal article:Umeharu Ohto, Takuma Shibata, Hiromi Tanji, Hanako Ishida, Elena Krayukhina, Susumu Uchiyama, Kensuke Miyake, and Toshiyuki Shimizu, “Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9″, Nature DOI: 10.1038/nature14138