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Open data
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Basic information
Entry | Database: PDB / ID: 7pgp | ||||||||||||
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Title | The core structure of human neurofibromin isoform 2 | ||||||||||||
![]() | Neurofibromin![]() | ||||||||||||
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Function / homology | ![]() positive regulation of mast cell apoptotic process / negative regulation of Rac protein signal transduction / regulation of glial cell differentiation / gamma-aminobutyric acid secretion, neurotransmission / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | Naschberger, A. / Baradaran, R. / Carroni, M. / Rupp, B. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: The structure of neurofibromin isoform 2 reveals different functional states. Authors: Andreas Naschberger / Rozbeh Baradaran / Bernhard Rupp / Marta Carroni / ![]() ![]() ![]() 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 ...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). 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 Å. The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing 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 membrane. 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. | ||||||||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 648.9 KB | Display | ![]() |
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PDB format | ![]() | 505.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 13391MC ![]() 7pgqC ![]() 7pgrC ![]() 7pgsC ![]() 7pgtC ![]() 7pguC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | ![]() Mass: 319757.656 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: Homo-dimer of human Neurofibromin Isoform 2 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 640 kDa/nm / Experimental value: YES |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 1 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Classification: refinement |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction![]() | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1165484 / Symmetry type: POINT |
Refinement | Cross valid method: THROUGHOUT |
Displacement parameters | Biso max: 136.26 Å2 / Biso mean: 78.3646 Å2 / Biso min: 34.24 Å2 |