1FYX

CRYSTAL STRUCTURE OF P681H MUTANT OF TIR DOMAIN OF HUMAN TLR2

1FYX の概要

• エントリーDOI: 10.2210/pdb1fyx/pdb
• 関連するPDBエントリー: 1FYV 1FYW
• 分子名称: TOLL-LIKE RECEPTOR 2 (1 entity in total)
• 機能のキーワード: beta-alpha-beta fold, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane ; Single-pass type I membrane protein : O60603
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18355.54

構造登録者

Xu, Y.,Tao, X.,Shen, B.,Horng, T.,Medzhitov, R.,Manley, J.L.,Tong, L. (登録日: 2000-10-03, 公開日: 2000-11-22, 最終更新日: 2024-10-30)

主引用文献

Xu, Y.,Tao, X.,Shen, B.,Horng, T.,Medzhitov, R.,Manley, J.L.,Tong, L.
Structural basis for signal transduction by the Toll/interleukin-1 receptor domains.
Nature, 408:111-115, 2000

PubMed Abstract: Toll-like receptors (TLRs) and the interleukin-1 receptor superfamily (IL-1Rs) are integral to both innate and adaptive immunity for host defence. These receptors share a conserved cytoplasmic domain, known as the TIR domain. A single-point mutation in the TIR domain of murine TLR4 (Pro712His, the Lps(d) mutation) abolishes the host immune response to lipopolysaccharide (LPS), and mutation of the equivalent residue in TLR2, Pro681His, disrupts signal transduction in response to stimulation by yeast and gram-positive bacteria. Here we report the crystal structures of the TIR domains of human TLR1 and TLR2 and of the Pro681His mutant of TLR2. The structures have a large conserved surface patch that also contains the site of the Lps(d) mutation. Mutagenesis and functional studies confirm that residues in this surface patch are crucial for receptor signalling. The Lps(d) mutation does not disturb the structure of the TIR domain itself. Instead, structural and functional studies indicate that the conserved surface patch may mediate interactions with the down-stream MyD88 adapter molecule, and that the Lps(d) mutation may abolish receptor signalling by disrupting this recruitment.

PubMed: 11081518
DOI: 10.1038/35047056

実験手法

X-RAY DIFFRACTION (2.8 Å)