2. Academic Validation
  3. TLR3 forms a laterally aligned multimeric complex along double-stranded RNA for efficient signal transduction

TLR3 forms a laterally aligned multimeric complex along double-stranded RNA for efficient signal transduction

  • Nat Commun. 2023 Jan 11;14(1):164. doi: 10.1038/s41467-023-35844-2.
Kentaro Sakaniwa # 1,  Akiko Fujimura # 1,  Takuma Shibata # 2,  Hideki Shigematsu 3 4,  Toru Ekimoto 5,  Masaki Yamamoto 3,  Mitsunori Ikeguchi 5 6,  Kensuke Miyake 2,  Umeharu Ohto 7,  Toshiyuki Shimizu 8
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
  • 2 Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
  • 3 RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo, Hyogo, 679-5148, Japan.
  • 4 Structural Biology Division, Japan Synchrotron Radiation Research Institute, 1-1-1 Kouto, Sayo, Hyogo, 679-5198, Japan.
  • 5 Computational Life Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
  • 6 HPC- and AI-driven Drug Development Platform Division, Center for Computational Science, RIKEN, Yokohama, 230-0045, Japan.
  • 7 Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. [email protected].
  • 8 Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. [email protected].
  • # Contributed equally.
PMID: 36631495 DOI: 10.1038/s41467-023-35844-2
Abstract

Toll-like Receptor 3 (TLR3) is a member of the TLR family, which plays an important role in the innate immune system and is responsible for recognizing viral double-stranded RNA (dsRNA). Previous biochemical and structural studies have revealed that a minimum length of approximately 40-50 base pairs of dsRNA is necessary for TLR3 binding and dimerization. However, efficient TLR3 activation requires longer dsRNA and the molecular mechanism underlying its dsRNA length-dependent activation remains unknown. Here, we report cryo-electron microscopy analyses of TLR3 complexed with longer dsRNA. TLR3 dimers laterally form a higher multimeric complex along dsRNA, providing the basis for cooperative binding and efficient signal transduction.

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