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

Author

Listed:
  • Kentaro Sakaniwa

    (The University of Tokyo, 7-3-1 Hongo)

  • Akiko Fujimura

    (The University of Tokyo, 7-3-1 Hongo)

  • Takuma Shibata

    (The University of Tokyo, 4-6-1 Shirokanedai)

  • Hideki Shigematsu

    (RIKEN SPring-8 Center, 1-1-1 Kouto
    Japan Synchrotron Radiation Research Institute)

  • Toru Ekimoto

    (Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku)

  • Masaki Yamamoto

    (RIKEN SPring-8 Center, 1-1-1 Kouto)

  • Mitsunori Ikeguchi

    (Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku
    HPC- and AI-driven Drug Development Platform Division, Center for Computational Science, RIKEN)

  • Kensuke Miyake

    (The University of Tokyo, 4-6-1 Shirokanedai)

  • Umeharu Ohto

    (The University of Tokyo, 7-3-1 Hongo)

  • Toshiyuki Shimizu

    (The University of Tokyo, 7-3-1 Hongo)

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.

Suggested Citation

  • Kentaro Sakaniwa & Akiko Fujimura & Takuma Shibata & Hideki Shigematsu & Toru Ekimoto & Masaki Yamamoto & Mitsunori Ikeguchi & Kensuke Miyake & Umeharu Ohto & Toshiyuki Shimizu, 2023. "TLR3 forms a laterally aligned multimeric complex along double-stranded RNA for efficient signal transduction," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35844-2
    DOI: 10.1038/s41467-023-35844-2
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    References listed on IDEAS

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    1. Lena Alexopoulou & Agnieszka Czopik Holt & Ruslan Medzhitov & Richard A. Flavell, 2001. "Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3," Nature, Nature, vol. 413(6857), pages 732-738, October.
    2. Chan Seok Lim & Yoon Ha Jang & Ga Young Lee & Gu Min Han & Hye Jin Jeong & Ji Won Kim & Jie-Oh Lee, 2022. "TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
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