8SPA

Structural insights into cellular control of the human CPEB3 prion, functionally regulated by a labile-amyloid-forming segment

8SPA の概要

• エントリーDOI: 10.2210/pdb8spa/pdb
• EMDBエントリー: 40677
• 分子名称: Cytoplasmic polyadenylation element-binding protein 3 (1 entity in total)
• 機能のキーワード: prion, amyloid, reversible, helical, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 26398.81

構造登録者

Flores, M.D.,Sawaya, M.R.,Boyer, D.R.,Zink, S.,Fioriti, L.,Rodriguez, J.A. (登録日: 2023-05-02, 公開日: 2024-05-08, 最終更新日: 2026-03-11)

主引用文献

Flores, M.D.,Sawaya, M.R.,Boyer, D.R.,Zink, S.,Tovmasyan, S.,Saucedo, A.,Richards, L.S.,Zee, C.T.,Cardenas, J.,Fioriti, L.,Rodriguez, J.A.
Structural insights into functional regulation of the human CPEB3 prion by an amyloid-forming segment.
Structure, 33:1314-1324.e5, 2025

PubMed Abstract: The cytoplasmic polyadenylation-element-binding-protein-3 (CPEB3) is a functional prion thought to modulate protein synthesis and enable consolidation of long-term memory in neurons. We report a cryoelectron microscopy (cryo-EM) structure of amyloid fibrils grown in vitro from the first prion-like domain of human CPEB3 (hCPEB3), revealing their ordered 49-residue core, spanning L103 to F151. CPEB3 lacking that segment coalesces into abnormal puncta in cells compared to wild-type CPEB3, localizes away from dormant p-bodies and toward stress granules, and lacks the ability to influence protein synthesis in neurons. Fluorescence-guided cryo-focused ion beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) applied to neuronal cells expressing CPEB3 reveal CPEB3-GFP signal from lamellae enriched in multivesicular bodies (MVBs), cavernous multilamellar compartments, and bundled filaments, suggesting a state of induced cellular stress. Accordingly, cells expressing wild-type CPEB3 are less viable than those expressing CPEB3 without its amyloid core, suggesting human CPEB3 regulation may be required to overcome the liability associated with its self-assembly in cells.

PubMed: 40480223
DOI: 10.1016/j.str.2025.05.007

実験手法

ELECTRON MICROSCOPY (3 Å)