7DAS

Mouse Toll-like receptor 3 ectodomain in complex with lncRNA Rmrp in lapped form

7DAS の概要

• エントリーDOI: 10.2210/pdb7das/pdb
• EMDBエントリー: 30626
• 分子名称: Toll-like receptor 3, RNA component of mitochondrial RNAase P (Rmrp), RNase MRP RNA (2 entities in total)
• 機能のキーワード: complex, innate immune system, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 204327.82

構造登録者

Li, B.,Cao, X. (登録日: 2020-10-18, 公開日: 2021-10-20, 最終更新日: 2025-09-17)

主引用文献

Zhang, S.,Li, B.,Liu, L.,Gong, D.,Zhang, D.,Liu, F.,Yang, X.,Qin, H.,Kong, D.,Zhang, S.,Rao, Z.,Cao, X.
Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation.
Cell Res., 2025

PubMed Abstract: The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3. Furthermore, K42 residue of TLR3 is essential for binding to Rmrp and subsequent dimerization. Rmrp dissociates from TLR3 following endosomal acidification, generating a matured TLR3 dimer which is primed for innate recognition and activation. Myeloid-cell deficiency of Rmrp reduces TLR3 dimerization and attenuates TLR3-mediated antiviral responses against influenza A both in vitro and in vivo. These findings elucidate the structural mode of self RNA Rmrp-primed TLR3 dimerization and ready for efficient innate recognition on endosomal membrane, extending our knowledge of how membrane-associated TLRs pre-dimerize and suggesting a new function of subcellular localized self RNAs in empowering innate activation.

PubMed: 40915996
DOI: 10.1038/s41422-025-01178-5

実験手法

ELECTRON MICROSCOPY (3.64 Å)