4YZY

Crystal structures reveal transient PERK luminal domain tetramerization in ER stress signaling

4YZY の概要

• エントリーDOI: 10.2210/pdb4yzy/pdb
• 分子名称: Eukaryotic translation initiation factor 2-alpha kinase 3 (1 entity in total)
• 機能のキーワード: upr, er stress sensing, proteostasis, perk, dimer, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass type I membrane protein: Q9Z2B5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33509.50

構造登録者

Carrara, M.,Prischi, F.,Ali, M.M.U. (登録日: 2015-03-25, 公開日: 2015-05-13, 最終更新日: 2024-10-16)

主引用文献

Carrara, M.,Prischi, F.,Nowak, P.R.,Ali, M.M.
Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling.
Embo J., 34:1589-1600, 2015

PubMed Abstract: Stress caused by accumulation of misfolded proteins within the endoplasmic reticulum (ER) elicits a cellular unfolded protein response (UPR) aimed at maintaining protein-folding capacity. PERK, a key upstream component, recognizes ER stress via its luminal sensor/transducer domain, but the molecular events that lead to UPR activation remain unclear. Here, we describe the crystal structures of mammalian PERK luminal domains captured in dimeric state as well as in a novel tetrameric state. Small angle X-ray scattering analysis (SAXS) supports the existence of both crystal structures also in solution. The salient feature of the tetramer interface, a helix swapped between dimers, implies transient association. Moreover, interface mutations that disrupt tetramer formation in vitro reduce phosphorylation of PERK and its target eIF2α in cells. These results suggest that transient conversion from dimeric to tetrameric state may be a key regulatory step in UPR activation.

PubMed: 25925385
DOI: 10.15252/embj.201489183

実験手法

X-RAY DIFFRACTION (3.2 Å)