5FN4

Cryo-EM structure of gamma secretase in class 2 of the apo- state ensemble

5FN4 の概要

• エントリーDOI: 10.2210/pdb5fn4/pdb
• 関連するPDBエントリー: 5FN2 5FN3 5FN5
• EMDBエントリー: 3239
• 分子名称: Nicastrin, Presenilin-1, Gamma-secretase subunit APH-1A, ... (5 entities in total)
• 機能のキーワード: hydrolase
• 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: 174048.04

構造登録者

Bai, X.C.,Rajendra, E.,Yang, G.H.,Shi, Y.G.,Scheres, S.H.W. (登録日: 2015-11-10, 公開日: 2015-12-16, 最終更新日: 2024-10-23)

主引用文献

Bai, X.C.,Rajendra, E.,Yang, G.,Shi, Y.,Scheres, S.H.
Sampling the conformational space of the catalytic subunit of human gamma-secretase.
Elife, 4:-, 2015

PubMed Abstract: Human γ-secretase is an intra-membrane protease that cleaves many different substrates. Aberrant cleavage of Notch is implicated in cancer, while abnormalities in cutting amyloid precursor protein lead to Alzheimer's disease. Our previous cryo-EM structure of γ-secretase revealed considerable disorder in its catalytic subunit presenilin. Here, we describe an image classification procedure that characterizes molecular plasticity at the secondary structure level, and apply this method to identify three distinct conformations in our previous sample. In one of these conformations, an additional transmembrane helix is visible that cannot be attributed to the known components of γ-secretase. In addition, we present a γ-secretase structure in complex with the dipeptidic inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). Our results reveal how conformational mobility in the second and sixth transmembrane helices of presenilin is greatly reduced upon binding of DAPT or the additional helix, and form the basis for a new model of how substrate enters the transmembrane domain.

PubMed: 26623517
DOI: 10.7554/eLife.11182

実験手法

ELECTRON MICROSCOPY (4 Å)