ArticleNature2014
Three-dimensional structure of human γ-secretase.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers.
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Who cites it
185 citing papers in PubMed.
- Soluble B-cell maturation antigen as a biomarker of progression and treatment response in patients with myeloma precursors.Blood neoplasia · 2026Article
- Structural principles underlying the evolution of SWI/SNF chromatin remodelers.Science advances · 2026Article
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Structural basis of sex pheromone detection in aphids.Cell research · 2026Article
- Molecular mechanisms of flotillin complexes in organizing membrane microdomains.Nature communications · 2026Article
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chromosome-level assembly and analysis of three hydroxy fatty acid-producing Physaria species.Nature communications · 2025Article
- Intravenous administration of blood-brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system.Nature biotechnology · 2025Article
- Alzheimer's Disease: From Molecular Mechanisms to Promising Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Pore Formation by Pore Forming Proteins in Lipid Membranes: Structural Insights Through Cryo-EM.The Journal of membrane biology · 2025Review
- γ-Secretase-Mediated Endoproteolysis of Neuregulin-1 and E-Cadherin.Biochemistry · 2025Article
- Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.Chembiochem : a European journal of chemical biology · 2025Review
- Structural basis of human γ-secretase inhibition by anticancer clinical compounds.Nature structural & molecular biology · 2025Article
- Effects of Transmembrane Phenylalanine Residues on γ-Secretase-Mediated Notch-1 Proteolysis.ACS chemical neuroscience · 2025Article
- Article
- Advancements in the conservation of the conformational epitope of membrane protein immunogens.Frontiers in immunology · 2025Review
- Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.Molecular brain · 2024Review
- Alzheimer-mutant γ-secretase complexes stall amyloid β-peptide production.bioRxiv : the preprint server for biology · 2024Article
- Notch signaling without the APH-2/nicastrin subunit of gamma secretase in Caenorhabditis elegans germline stem cells.Genetics · 2024Article
- Structural basis for EROS binding to human phagocyte NADPH oxidase NOX2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
125 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.