5A63

Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution.

「4UPC」から置き換えられました

5A63 の概要

• エントリーDOI: 10.2210/pdb5a63/pdb
• EMDBエントリー: 3061
• 分子名称: Nicastrin, Presenilin-1, Gamma-secretase subunit APH-1A, ... (8 entities in total)
• 機能のキーワード: hydrolase, cryo-em, human gamma-secretase, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 177972.24

構造登録者

Bai, X.,Yan, C.,Yang, G.,Lu, P.,Ma, D.,Sun, L.,Zhou, R.,Scheres, S.H.W.,Shi, Y. (登録日: 2015-06-24, 公開日: 2015-08-05, 最終更新日: 2024-11-13)

主引用文献

Bai, X.,Yan, C.,Yang, G.,Lu, P.,Ma, D.,Sun, L.,Zhou, R.,Scheres, S.H.W.,Shi, Y.
An Atomic Structure of Human Gamma-Secretase
Nature, 525:212-, 2015

PubMed Abstract: Dysfunction of the intramembrane protease γ-secretase is thought to cause Alzheimer's disease, with most mutations derived from Alzheimer's disease mapping to the catalytic subunit presenilin 1 (PS1). Here we report an atomic structure of human γ-secretase at 3.4 Å resolution, determined by single-particle cryo-electron microscopy. Mutations derived from Alzheimer's disease affect residues at two hotspots in PS1, each located at the centre of a distinct four transmembrane segment (TM) bundle. TM2 and, to a lesser extent, TM6 exhibit considerable flexibility, yielding a plastic active site and adaptable surrounding elements. The active site of PS1 is accessible from the convex side of the TM horseshoe, suggesting considerable conformational changes in nicastrin extracellular domain after substrate recruitment. Component protein APH-1 serves as a scaffold, anchoring the lone transmembrane helix from nicastrin and supporting the flexible conformation of PS1. Ordered phospholipids stabilize the complex inside the membrane. Our structure serves as a molecular basis for mechanistic understanding of γ-secretase function.

PubMed: 26280335
DOI: 10.1038/NATURE14892

実験手法

ELECTRON MICROSCOPY (3.4 Å)