6IYC

Recognition of the Amyloid Precursor Protein by Human gamma-secretase

6IYC の概要

• エントリーDOI: 10.2210/pdb6iyc/pdb
• EMDBエントリー: 9751
• 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: 191217.04

構造登録者

Zhou, R.,Yang, G.,Guo, X.,Zhou, Q.,Lei, J.,Shi, Y. (登録日: 2018-12-14, 公開日: 2019-01-23, 最終更新日: 2025-04-09)

主引用文献

Zhou, R.,Yang, G.,Guo, X.,Zhou, Q.,Lei, J.,Shi, Y.
Recognition of the amyloid precursor protein by human gamma-secretase.
Science, 363:-, 2019

PubMed Abstract: Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a transmembrane (TM) APP fragment at 2.6-angstrom resolution. The TM helix of APP closely interacts with five surrounding TMs of PS1 (the catalytic subunit of γ-secretase). A hybrid β sheet, which is formed by a β strand from APP and two β strands from PS1, guides γ-secretase to the scissile peptide bond of APP between its TM and β strand. Residues at the interface between PS1 and APP are heavily targeted by recurring mutations from AD patients. This structure, together with that of γ-secretase bound to Notch, reveal contrasting features of substrate binding, which may be applied toward the design of substrate-specific inhibitors.

PubMed: 30630874
DOI: 10.1126/science.aaw0930

実験手法

ELECTRON MICROSCOPY (2.6 Å)