4UIS

The cryoEM structure of human gamma-Secretase complex

4UIS の概要

• エントリーDOI: 10.2210/pdb4uis/pdb
• EMDBエントリー: 2974
• 分子名称: GAMMA-SECRETASE, LYSOZYME, ... (5 entities in total)
• 機能のキーワード: hydrolase, gamma-secretase
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Host cytoplasm : A0A097J809
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 127307.88

構造登録者

Sun, L.,Zhao, L.,Yang, G.,Yan, C.,Zhou, R.,Zhou, X.,Xie, T.,Zhao, Y.,Wu, S.,Li, X.,Shi, Y. (登録日: 2015-04-03, 公開日: 2015-06-10, 最終更新日: 2024-11-13)

主引用文献

Sun, L.,Zhao, L.,Yang, G.,Yan, C.,Zhou, R.,Zhou, X.,Xie, T.,Zhao, Y.,Wu, S.,Li, X.,Shi, Y.
Structural Basis of Human Gamma-Secretase Assembly.
Proc.Natl.Acad.Sci.USA, 112:6003-, 2015

PubMed Abstract: The four-component intramembrane protease γ-secretase is intricately linked to the development of Alzheimer's disease. Despite recent structural advances, the transmembrane segments (TMs) of γ-secretase remain to be specifically assigned. Here we report a 3D structure of human γ-secretase at 4.32-Å resolution, determined by single-particle, electron cryomicroscopy in the presence of digitonin and with a T4 lysozyme fused to the amino terminus of presenilin 1 (PS1). The overall structure of this human γ-secretase is very similar to that of wild-type γ-secretase determined in the presence of amphipols. The 20 TMs are unambiguously assigned to the four components, revealing principles of subunit assembly. Within the transmembrane region, PS1 is centrally located, with its amino-terminal fragment (NTF) packing against Pen-2 and its carboxyl-terminal fragment (CTF) interacting with Aph-1. The only TM of nicastrin associates with Aph-1 at the thick end of the TM horseshoe, and the extracellular domain of nicastrin directly binds Pen-2 at the thin end. TM6 and TM7 in PS1, which harbor the catalytic aspartate residues, are located on the convex side of the TM horseshoe. This structure serves as an important framework for understanding the function and mechanism of γ-secretase.

PubMed: 25918421
DOI: 10.1073/PNAS.1506242112

実験手法

ELECTRON MICROSCOPY (4.4 Å)