3W3L

Crystal structure of human TLR8 in complex with Resiquimod (R848) crystal form 1

3W3L の概要

• エントリーDOI: 10.2210/pdb3w3l/pdb
• 関連するPDBエントリー: 3W3G 3W3J 3W3K 3W3M 3W3N
• 分子名称: Toll-like receptor 8, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: leucine rich repeat, rna, glycosylation, rna recognition, ssrna, receptor, rna receptor, innate immunity, rna binding, secreted, resiquimod, antivirus and antitumor drug, antivirus and antitumor drug binding, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 386318.37

構造登録者

Tanji, H.,Ohto, U.,Shimizu, T. (登録日: 2012-12-22, 公開日: 2013-04-03, 最終更新日: 2024-10-30)

主引用文献

Tanji, H.,Ohto, U.,Shibata, T.,Miyake, K.,Shimizu, T.
Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands
Science, 339:1426-1429, 2013

PubMed Abstract: Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.

PubMed: 23520111
DOI: 10.1126/science.1229159

実験手法

X-RAY DIFFRACTION (2.33 Å)