ArticleScience advances2017
Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains.
Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Effects of Transmembrane Phenylalanine Residues on γ-Secretase-Mediated Notch-1 Proteolysis.ACS chemical neuroscience · 2025Article
- Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.Biophysical journal · 2025Article
- Optimizing NMR fragment-based drug screening for membrane protein targets.Journal of structural biology: X · 2024Article
- Lipid environment modulates processivity and kinetics of a presenilin homolog acting on multiple substrates in vitro.The Journal of biological chemistry · 2023Article
- OptIC-Notch reveals mechanism that regulates receptor interactions with CSL.Development (Cambridge, England) · 2023Article
- Cooperation of N- and C-terminal substrate transmembrane domain segments in intramembrane proteolysis by γ-secretase.Communications biology · 2023Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- Role of cholesterol in substrate recognition by [Formula: see text]-secretase.Scientific reports · 2021Article
- Multi-Arm PEG/Peptidomimetic Conjugate Inhibitors of DR6/APP Interaction Block Hematogenous Tumor Cell Extravasation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- The MemMoRF database for recognizing disordered protein regions interacting with cellular membranes.Nucleic acids research · 2021Article
- γ-Secretase cleavage of the Alzheimer risk factor TREM2 is determined by its intrinsic structural dynamics.The EMBO journal · 2020Article
- Side-by-side comparison of Notch- and C83 binding to γ-secretase in a complete membrane model at physiological temperature.RSC advances · 2020Article
- γ-Secretase Partitioning into Lipid Bilayers Remodels Membrane Microdomains after Direct Insertion.Langmuir : the ACS journal of surfaces and colloids · 2020Article
- The Implications for Cells of the Lipid Switches Driven by Protein-Membrane Interactions and the Development of Membrane Lipid Therapy.International journal of molecular sciences · 2020Review
- Engineering of an enhanced synthetic Notch receptor by reducing ligand-independent activation.Communications biology · 2020Article
- Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state.eLife · 2020Article
- Substrate-Enzyme Interactions in Intramembrane Proteolysis: γ-Secretase as the Prototype.Frontiers in molecular neuroscience · 2020Review
- Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.Biophysical journal · 2019Article
- Article
- Bexarotene Binds to the Amyloid Precursor Protein Transmembrane Domain, Alters Its α-Helical Conformation, and Inhibits γ-Secretase Nonselectively in Liposomes.ACS chemical neuroscience · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
γ-Secretase cleavage of the Notch receptor transmembrane domain is a critical signaling event for various cellular processes. Efforts to develop inhibitors of γ-secretase cleavage of the amyloid-β precursor C99 protein as potential Alzheimer's disease therapeutics have been confounded by toxicity resulting from the inhibition of normal cleavage of Notch. We present biochemical and structural data for the combined transmembrane and juxtamembrane Notch domains (Notch-TMD) that illuminate Notch signaling and that can be compared and contrasted with the corresponding traits of C99. The Notch-TMD and C99 have very different conformations, adapt differently to changes in model membrane hydrophobic span, and exhibit different cholesterol-binding properties. These differences may be exploited in the design of agents that inhibit cleavage of C99 while allowing Notch cleavage.
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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.