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Three-dimensional Structure of Human γ-secretase

Three-dimensional Structure of Human γ-secretase

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

Nature. 2014 Aug 14;512(7513):166-170.

PMID: 25043039

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248115	β-Secretase human			Price

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