SPring-8, the large synchrotron radiation facility

    A research group has succeeded for the first time in the world in clarifying the detailed crystal structures of TLR8 in complex with ssRNA. TLR8 activates the innate immune system by recognizing ssRNAs derived from pathogens. The research group was led by Toshiyuki Shimizu (professor), Hiromi Tanji (graduate student), and Umeharu Ohto (lecturer) of the Graduate School of Pharmaceutical Sciences, The University of Tokyo, and Kensuke Miyake (professor) and Takuma Shibata (assistant professor) of the Institute of Medical Science, The University of Tokyo.

Our bodies have an innate immune system that protects our bodies from pathogens. Toll-like receptor (TLR) proteins recognize pathogens and protect our bodies from pathogens by inducing an inflammatory reaction. Toll-like receptor 7 (TLR7) and TLR8 recognize ssRNAs derived from pathogens and are involved in the protection against viral infection and autoimmune diseases. However, the mechanism underlying the ssRNA recognition by TLR7 and TLR8 has remained unclarified.

The research group clarified the detailed crystal structures of TLR8 in complex with ssRNA in this study. The results revealed that TLR8 recognizes not only ssRNA but also a low-molecular-weight uridine,^*2 a degradation product of ssRNA, at different sites simultaneously. The coordinated interaction between ssRNA and uridine was found to be involved in the activation of TLR8. These findings will also clarify why TLR8 is activated by ssRNA, which is greatly different from RNA structurally and chemically.

The achievements of this study are expected to lead to the development of anticancer drugs targeting TLR8 and therapeutic agents for autoimmune diseases.

These achievements were realized in cooperation with another research group that was led by Toshiaki Isobe (specially appointed professor), Masato Taoka (assistant professor), and Yoshio Yamauchi (postdoctoral research scientist) of the Graduate School of Science and Technology, Tokyo Metropolitan University.

Publication:
"Toll-like receptor 8 senses degradation products of single-stranded RNA"
Authors: Hiromi Tanji*, Umeharu Ohto*, Takuma Shibata, Masato Taoka, Yoshio Yamauchi, Toshiaki Isobe, Kensuke Miyake, Toshiyuki Shimizu† (*first authors who contributed equally to this work, †leading author)
Nature Structural & Molecular Biology
DOI番号: 10.1038/nsmb.2943