{"entity": "researcher", "timestamp": "2026-09-24T14:47:11.981Z", "family": "Rupp", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-3300-6965", "affiliations": ["Institute of Genetic Epidemiology, Medical University Innsbruck, Innsbruck, Austria. br@hofkristallamt.org.", "k.-k. Hofkristallamt, San Diego, CA, USA. br@hofkristallamt.org."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/6925038ef977425492e6e9f7fec19ef1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/6925038ef977425492e6e9f7fec19ef1"}}, "publications": [{"entity": "publication", "iuid": "f4693aa12b5646cabf6e5b44d9f0ac69", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/f4693aa12b5646cabf6e5b44d9f0ac69.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/f4693aa12b5646cabf6e5b44d9f0ac69"}}, "title": "The structure of neurofibromin isoform 2 reveals different functional states.", "authors": [{"family": "Naschberger", "given": "Andreas", "initials": "A"}, {"family": "Baradaran", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-6096-9169", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/32ce7621095c4a8dad9b2eb95db1b738.json"}}, {"family": "Rupp", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-3300-6965", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6925038ef977425492e6e9f7fec19ef1.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/55fa4ba347a34d7ca80d214e8d718e44.json"}}], "type": "journal article", "published": "2021-11-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "599", "issue": "7884", "pages": "315-319", "issn-l": "0028-0836"}, "abstract": "The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1)1,2. As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. We determined the human Nf1 dimer structure at an overall resolution of 3.3 \u00c5. The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing3 isoform 2 in a closed, self-inhibited, Zn-stabilized state and an open state. In the closed conformation, HEAT/ARM core domains shield the GTPase-activating protein-related domain (GRD) so that Ras binding is sterically inhibited. In a distinctly different, open conformation of one protomer, a large-scale movement of the GRD occurs, which is necessary to access Ras, whereas Sec14-PH reorients to allow interaction with the cellular membrane4. Zn incubation of Nf1 leads to reduced Ras-GAP activity with both protomers in the self-inhibited, closed conformation stabilized by a Zn binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker. The transition between closed, self-inhibited states of Nf1 and open states provides guidance for targeted studies deciphering the complex molecular mechanism behind the widespread neurofibromatosis syndrome and Nf1 dysfunction in carcinogenesis.", "doi": "10.1038/s41586-021-04024-x", "pmid": "34707296", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8580823"}, {"db": "pii", "key": "10.1038/s41586-021-04024-x"}], "notes": [], "created": "2026-09-23T08:35:40.911Z", "modified": "2026-09-23T08:35:41.035Z"}]}