ArticleProceedings of the National Academy of Sciences of the United States of America2021
Notch-Jagged signaling complex defined by an interaction mosaic.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- The dual-enhanced graph learning framework DePass allows paired data integration in single-cell and spatial multiomics.Nature cell biology · 2026Article
- Review
- Azvudine Suppresses Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma by Targeting the Notch-HEY Signalling Pathway.International journal of molecular sciences · 2025Article
- Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.Biophysical journal · 2025Article
- Structural and functional studies of the EGF20-27 region reveal new features of the human Notch receptor important for optimal activation.Structure (London, England : 1993) · 2024Article
- Tight junction protein LSR is a host defense factor against SARS-CoV-2 infection in the small intestine.The EMBO journal · 2024Article
- Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force.Nature communications · 2024Article
- Toll-like receptors as a missing link in Notch signaling cascade during neurodevelopment.Frontiers in molecular neuroscience · 2024Article
- Coordination of host and endosymbiont gene expression governs endosymbiont growth and elimination in the cereal weevil Sitophilus spp.Microbiome · 2023Article
- Human aortic smooth muscle cell regulation by METTL3 via upregulation of m6A NOTCH1 modification and inhibition of NOTCH1.Annals of translational medicine · 2023Article
- The cellular uncertainty in thoracic aortic dissections: the roles of METTL3 and NOTCH1 on m6A in human aortic smooth muscle cells.Annals of translational medicine · 2023Article
- A new model of Notch signalling: Control of Notch receptor cis-inhibition via Notch ligand dimers.PLoS computational biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Notch signaling system links cellular fate to that of its neighbors, driving proliferation, apoptosis, and cell differentiation in metazoans, whereas dysfunction leads to debilitating developmental disorders and cancers. Other than a five-by-five domain complex, it is unclear how the 40 extracellular domains of the Notch1 receptor collectively engage the 19 domains of its canonical ligand, Jagged1, to activate Notch1 signaling. Here, using cross-linking mass spectrometry (XL-MS), biophysical, and structural techniques on the full extracellular complex and targeted sites, we identify five distinct regions, two on Notch1 and three on Jagged1, that form an interaction network. The Notch1 membrane-proximal regulatory region individually binds to the established Notch1 epidermal growth factor (EGF) 8-EGF13 and Jagged1 C2-EGF3 activation sites as well as to two additional Jagged1 regions, EGF8-EGF11 and cysteine-rich domain. XL-MS and quantitative interaction experiments show that the three Notch1-binding sites on Jagged1 also engage intramolecularly. These interactions, together with Notch1 and Jagged1 ectodomain dimensions and flexibility, determined by small-angle X-ray scattering, support the formation of nonlinear architectures. Combined, the data suggest that critical Notch1 and Jagged1 regions are not distal but engage directly to control Notch1 signaling, thereby redefining the Notch1-Jagged1 activation mechanism and indicating routes for therapeutic applications.
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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.