5IJD

The crystal structure of mouse TLR4/MD-2/lipid A complex

「5HG6」から置き換えられました

5IJD の概要

• エントリーDOI: 10.2210/pdb5ijd/pdb
• 関連するPDBエントリー: 5LJB 5LJC
• 分子名称: Toll-like receptor 4, Variable lymphocyte receptor B chimera, Lymphocyte antigen 96, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: immune response, protein complex, natural agonist, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 177128.66

構造登録者

Wang, Y.,Su, L.,Morin, M.D.,Jones, B.T.,Whitby, L.R.,Surakattula, M.,Huang, H.,Shi, H.,Choi, J.H.,Wang, K.,Moresco, E.M.,Berger, M.,Zhan, X.,Zhang, H.,Boger, D.L.,Beutler, B. (登録日: 2016-03-01, 公開日: 2016-04-27, 最終更新日: 2024-10-30)

主引用文献

Wang, Y.,Su, L.,Morin, M.D.,Jones, B.T.,Whitby, L.R.,Surakattula, M.M.,Huang, H.,Shi, H.,Choi, J.H.,Wang, K.W.,Moresco, E.M.,Berger, M.,Zhan, X.,Zhang, H.,Boger, D.L.,Beutler, B.
TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS.
Proc.Natl.Acad.Sci.USA, 113:E884-E893, 2016

PubMed Abstract: Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-Å resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.

PubMed: 26831104
DOI: 10.1073/pnas.1525639113

実験手法

X-RAY DIFFRACTION (2.7 Å)