6I3N

Helical MyD88 death domain filament

6I3N の概要

• エントリーDOI: 10.2210/pdb6i3n/pdb
• EMDBエントリー: 4405
• 分子名称: Myeloid differentiation primary response protein MyD88 (1 entity in total)
• 機能のキーワード: helix, filament, tlr, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 229409.35

構造登録者

Moncrieffe, M.C.,Bollschweiler, D.,Penczek, P.A.P.,Gay, N.J. (登録日: 2018-11-06, 公開日: 2019-11-20, 最終更新日: 2024-05-15)

主引用文献

Moncrieffe, M.C.,Bollschweiler, D.,Li, B.,Penczek, P.A.,Hopkins, L.,Bryant, C.E.,Klenerman, D.,Gay, N.J.
MyD88 Death-Domain Oligomerization Determines Myddosome Architecture: Implications for Toll-like Receptor Signaling.
Structure, 28:281-289.e3, 2020

PubMed Abstract: Toll-like receptors (TLRs) are pivotal in triggering the innate immune response to pathogen infection. Ligand binding induces receptor dimerization which facilitates the recruitment of other post-receptor signal transducers into a complex signalosome, the Myddosome. Central to this process is Myeloid differentiation primary response 88 (MyD88), which is required by almost all TLRs, and signaling is thought to proceed via the stepwise, sequential assembly of individual components. Here, we show that the death domains of human MyD88 spontaneously and reversibly associate to form helical filaments in vitro. A 3.1-Å cryoelectron microscopy structure reveals that the architecture of the filament is identical to that of the 6:4 MyD88-IRAK4-IRAK2 hetero-oligomeric Myddosome. Additionally, the death domain of IRAK4 interacts with the filaments to reconstitute the non-stoichiometric 6:4 MyD88-IRAK4 complex. Together, these data suggest that intracellularly, the MyD88 scaffold may be pre-formed and poised for recruitment of IRAKs on receptor activation and TIR engagement.

PubMed: 31995744
DOI: 10.1016/j.str.2020.01.003

実験手法

ELECTRON MICROSCOPY (3.1 Å)