Details

Autor(en) / Beteiligte

• Lu, Peilong
• Bai, Xiao-Chen
• Ma, Dan
• Xie, Tian
• Yan, Chuangye
• Sun, Linfeng
• Yang, Guanghui
• Zhao, Yanyu
• Zhou, Rui
• Scheres, Sjors H W
• Shi, Yigong

Titel

Three-dimensional structure of human γ-secretase

Ist Teil von

• Nature (London), 2014-08, Vol.512 (7513), p.166-170

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2014

Link zum Volltext

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• The γ-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a membrane-embedded protease that controls a number of important cellular functions through substrate cleavage. Aberrant cleavage of the amyloid precursor protein (APP) results in aggregation of amyloid-β, which accumulates in the brain and consequently causes Alzheimer's disease. Here we report the three-dimensional structure of an intact human γ-secretase complex at 4.5 Å resolution, determined by cryo-electron-microscopy single-particle analysis. The γ-secretase complex comprises a horseshoe-shaped transmembrane domain, which contains 19 transmembrane segments (TMs), and a large extracellular domain (ECD) from nicastrin, which sits immediately above the hollow space formed by the TM horseshoe. Intriguingly, nicastrin ECD is structurally similar to a large family of peptidases exemplified by the glutamate carboxypeptidase PSMA. This structure serves as an important basis for understanding the functional mechanisms of the γ-secretase complex.