ArticleNature2019
Structural basis of Notch recognition by human γ-secretase.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
What it found
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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.
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Who cites it
143 citing papers in PubMed, 162 citations in OpenAlex.
- Article
- Single-Nucleus Transcriptomes of Lacrimal Gland Adenoid Cystic Carcinoma With Different Growth Patterns.Head & neck · 2026Article
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Transmembrane domain switching controls PINK1 import and fate in mitochondria.The EMBO journal · 2026Article
- miR-151-5p regulates neural stem cell fate by targeting APH1A to modulate Notch signaling gradients.Stem cell reports · 2026Article
- From mechanistic modeling to AI-driven design: computational strategies for targeting the γ-secretase complex.Briefings in bioinformatics · 2026Review
- Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters.Chemical reviews · 2026Review
- Evidence that extra copies of chromosome 1q play a role in the early phases of pancreatic neoplasia.Science advances · 2026Article
- A C. elegans model of familial Alzheimer's disease shows age-dependent synaptic degeneration independent of amyloid β-peptide.Neurobiology of disease · 2026Article
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibitory proteins ofJournal of bacteriology · 2025Article
- Transient cholesterol interactions with the amyloid precursor protein involved in Alzheimer's disease pathogenesis.Biophysical reviews · 2025Review
- A unique subpopulation of wild-type neurons recapitulating familial Alzheimer's disease phenotypes.Cell death & disease · 2025Article
- Charting γ-secretase substrates by explainable AI.Nature communications · 2025Article
- Advances in the Exploration of Coordination Complexes of Vanadium in the Realm of Alzheimer's Disease: A Mini Review.Molecules (Basel, Switzerland) · 2025Review
- 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
- Signaling pathways and molecular mechanisms involved in the onset and progression of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); a focus on Notch3 signaling.The journal of headache and pain · 2025Review
- Structural basis of human γ-secretase inhibition by anticancer clinical compounds.Nature structural & molecular biology · 2025Article
83 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
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase.
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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 Socratic graph.