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Updated: Apr 26, 2026

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
Published on: June 24, 2025
Three-dimensional structure of human γ-secretase
Peilong Lu1,2, Xiao-Chen Bai3, Dan Ma1,2
1Ministry of Education Key Laboratory of Protein Science, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.
The study reveals the 3D structure of the human gamma-secretase complex, crucial for cellular functions. This finding provides insights into Alzheimer
Area of Science:
- Biochemistry
- Structural Biology
- Neuroscience
Background:
- The gamma-secretase complex is a membrane-embedded protease essential for cellular functions.
- Dysfunctional cleavage of amyloid precursor protein (APP) by gamma-secretase leads to amyloid-beta aggregation and Alzheimer's disease.
Purpose of the Study:
- To determine the three-dimensional structure of the intact human gamma-secretase complex.
- To provide a structural basis for understanding the complex's functional mechanisms.
Main Methods:
- Cryo-electron microscopy single-particle analysis was used.
- The study determined the structure at 4.5 Å resolution.
Main Results:
- The human gamma-secretase complex has a horseshoe-shaped transmembrane domain with 19 transmembrane segments.
- A large extracellular domain from nicastrin is situated above the transmembrane domain's hollow space.
- The nicastrin extracellular domain shows structural similarity to peptidases like glutamate carboxypeptidase.
Conclusions:
- The determined structure offers a foundational understanding of gamma-secretase complex function.
- This structural information is vital for future research into Alzheimer's disease mechanisms and potential therapeutics.
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Published on: January 25, 2018
14:55Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
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