ArticleNature structural & molecular biology2021
The cryo-EM structure of the human neurofibromin dimer reveals the molecular basis for neurofibromatosis type 1.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 56 citations in OpenAlex.
- Relation Between Genotype and Behavioral Phenotype in Children and Adolescents With Neurofibromatosis Type 1.JAACAP open · 2026Article
- Prime Editing-Based Functional Characterization Supports a Likely Pathogenic Interpretation ofGenes · 2026Article
- Recent breakthroughs in understanding the allosteric features of Ras GTPases and their effector and regulatory protein interactions, enabling drug design.Current opinion in structural biology · 2026Review
- Review
- Current states in understanding oligodendroglia-mediated neurological issues in neurofibromatosis type 1 (NF1).Acta neuropathologica communications · 2025Review
- Development of an adeno-associated virus vector for gene replacement therapy of NF1-related tumors.Nature communications · 2025Article
- Global proteomics and affinity mass spectrometry analysis of human Schwann cells indicates that variation in and loss of neurofibromin (NF1) alters protein expression and cellular and mitochondrial metabolism.Scientific reports · 2025Article
- Unmasking AlphaFold to integrate experiments and predictions in multimeric complexes.Nature communications · 2024Article
- Article
- Schwann cell derived pleiotrophin stimulates fibroblast for proliferation and excessive collagen deposition in plexiform neurofibroma.Cancer gene therapy · 2024Article
- Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance.Nature communications · 2024Article
- Article
- New insights into the molecular basis of spinal neurofibromatosis type 1.European journal of human genetics : EJHG · 2023Article
- RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.The Journal of investigative dermatology · 2023Review
- The oncogenic role of NF1 in gallbladder cancer through regulation of YAP1 stability by direct interaction with YAP1.Journal of translational medicine · 2023Article
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Arabidopsis Sec14 proteins (SFH5 and SFH7) mediate interorganelle transport of phosphatidic acid and regulate chloroplast development.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Functional Assays Combined with Pre-mRNA-Splicing Analysis Improve Variant Classification and Diagnostics for Individuals with Neurofibromatosis Type 1 and Legius Syndrome.Human mutation · 2023Article
- Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism.Nature structural & molecular biology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurofibromin (NF1) mutations cause neurofibromatosis type 1 and drive numerous cancers, including breast and brain tumors. NF1 inhibits cellular proliferation through its guanosine triphosphatase-activating protein (GAP) activity against rat sarcoma (RAS). In the present study, cryo-electron microscope studies reveal that the human ~640-kDa NF1 homodimer features a gigantic 30 × 10 nm array of α-helices that form a core lemniscate-shaped scaffold. Three-dimensional variability analysis captured the catalytic GAP-related domain and lipid-binding SEC-PH domains positioned against the core scaffold in a closed, autoinhibited conformation. We postulate that interaction with the plasma membrane may release the closed conformation to promote RAS inactivation. Our structural data further allow us to map the location of disease-associated NF1 variants and provide a long-sought-after structural explanation for the extreme susceptibility of the molecule to loss-of-function mutations. Collectively these findings present potential new routes for therapeutic modulation of the RAS pathway.
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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.