Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
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.
Nat Commun. 2023 Jan 11;14(1):164. doi: 10.1038/s41467-023-35844-2.
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.
Toll 样受体 3（TLR3）是 TLR 家族的成员，在先天免疫系统中发挥重要作用，负责识别病毒双链 RNA（dsRNA）。先前的生化和结构研究表明，TLR3 结合和二聚化所需的 dsRNA 最小长度约为 40-50 个碱基对。然而，有效的 TLR3 激活需要更长的 dsRNA，其 dsRNA 长度依赖性激活的分子机制尚不清楚。在这里，我们报告了 TLR3 与更长 dsRNA 复合的低温电子显微镜分析。TLR3 二聚体沿 dsRNA 侧向形成更高的多聚体复合物，为协同结合和有效信号转导提供了基础。
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