ArticleNature2015
An atomic structure of human γ-secretase.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 274 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
274 citing papers in PubMed, 1 synthesis or guideline pooled it, 516 citations in OpenAlex.
- γ-Secretase Genetics of Hidradenitis Suppurativa: A Systematic Literature Review.Dermatology (Basel, Switzerland) · 2021Pooled it
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- In Silico Structure-Guided Design of Peptide Candidates Targeting γ-Secretase Subunit Assembly.Proteins · 2026Article
- Interactive segmentation of membrane and membrane-mimic densities in cryo-EM maps.Acta crystallographica. Section D, Structural biology · 2026Article
- Dimeric architecture and membrane thinning govern substrate recognition by human signal peptide peptidase.Research square · 2026Article
- From mechanistic modeling to AI-driven design: computational strategies for targeting the γ-secretase complex.Briefings in bioinformatics · 2026Review
- Breaking barriers: transitioning from X-ray crystallography to cryo-EM for structural studies.Acta crystallographica. Section D, Structural biology · 2026Article
- Interpretable machine-learning prediction of PSEN1 missense variant pathogenicity based on multi-omics enrichment in six core Alzheimer's disease genes.Alzheimer's research & therapy · 2026Article
- Article
- Advances in Crystallography and Cryo-Electron Microscopy for the Study of Membrane Proteins.Advances in experimental medicine and biology · 2026Review
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- Biological Breakthroughs and Drug Discovery Revolution via Cryo-Electron Microscopy of Membrane Proteins.Membranes · 2025Review
- Restoring amyloid-β42 and γ-secretase function in Alzheimer's disease.Brain : a journal of neurology · 2025Review
- Intravenous administration of blood-brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system.Nature biotechnology · 2025Article
- Breaking Barriers: Transitioning from X-ray Crystallography to Cryo-EM for Structural Studies of ATAD2B.bioRxiv : the preprint server for biology · 2025Article
- Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.Chembiochem : a European journal of chemical biology · 2025Review
- The N-terminal PA domains of signal-peptide-peptidase-like 2 (SPPL2) proteases impact on TNFα cleavage.Communications biology · 2025Article
- Structural basis of human γ-secretase inhibition by anticancer clinical compounds.Nature structural & molecular biology · 2025Article
- Comprehensive investigation of multiple targets in the development of newer drugs for the Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
214 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
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.
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What OpenQuestion holds
Registered trials
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.