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

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.

SUBMITTER: Sakaniwa K

PROVIDER: S-EPMC9834221 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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

Sakaniwa Kentaro K Fujimura Akiko A Shibata Takuma T Shigematsu Hideki H Ekimoto Toru T Yamamoto Masaki M Ikeguchi Mitsunori M Miyake Kensuke K Ohto Umeharu U Shimizu Toshiyuki T

Nature communications 20230111 1

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 ...[more]

PMID: 36631495

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