6IDF

Cryo-EM structure of gamma secretase in complex with a Notch fragment

6IDF の概要

• エントリーDOI: 10.2210/pdb6idf/pdb
• EMDBエントリー: 3061 3237 3238 3239 3240 9648
• 分子名称: Nicastrin, CHOLESTEROL, Presenilin-1, ... (10 entities in total)
• 機能のキーワード: complex, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 195623.20

構造登録者

Yang, G.,Zhou, R.,Zhou, Q.,Guo, X.,Yan, C.,Ke, M.,Lei, J.,Shi, Y. (登録日: 2018-09-09, 公開日: 2018-12-26, 最終更新日: 2025-09-17)

主引用文献

Yang, G.,Zhou, R.,Zhou, Q.,Guo, X.,Yan, C.,Ke, M.,Lei, J.,Shi, Y.
Structural basis of Notch recognition by human gamma-secretase
Nature, 565:192-197, 2019

PubMed Abstract: Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase.

PubMed: 30598546
DOI: 10.1038/s41586-018-0813-8

実験手法

ELECTRON MICROSCOPY (2.7 Å)