Neurofibromin

spinqualitylabelsall models Neurofibromin Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Introduction Neurofibromin is a cytoplasmic protein located close to the cell membrane that is encoded by the NF1 gene located on chromosome 17 . It is a suppressor of the Ras oncogene through its effect on the rate of catalysis from Ras-GTP (active) to Ras-GDP (inactive). NF increasing the rate of catalysis of Ras means that Ras spends more time in its inactive state and cannot cause unnecessary cell proliferation linked to cancer. Structure Important Structural Features Arginine Finger The catalytic glutamine is too far away in the GDP bound form to perform any function. The arginine finger stabilizes glutamine which assists the cleaving mechanism. RAS Complex NF interacts with Ras to form a complex. R68 assists N61 in catalysis. Mechanism of Ras Coupled with Neurofibromin The RasGAP interactions that occur when neurofibromin's GAP domain and Ras are bound have two critical catalytic components. The first is the the arginine finger of the NF protein, which stabilizes the catalytic glutamine, as well as stabilizing the transition state of the phosphoryl transfer. The second component is the catalytic glutamine of the Ras protein, which stabilizes the nucleophilic water as it attacks the third phosphate group in the GTP molecule as shown in Figure 1. Figure 1: The catalytic glutamine stabilizes the nucleophilic water. Downstream Effects Figure X; By cybertory - This file was derived from: Signal transduction v1.png, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12081090 Disease Relevance Mutations to the neurofibromin protein are implicated in the progression of Neurofibromatosis type 1 (NF1). This condition drives several forms of human cancers by inactivating the Ras suppression effects of NF, allowing Ras to behave as an oncogene. Neurofibromatosis type 1 is an autosomal dominant disorder that affects 1 in 3,000 people, and the NF gene itself has the highest mutation rate of any known human gene, adding to its prevalence. NF1 primarily causes tumors in the central and peripheral nervous systems, but often has a multisystem expression including tumors in the dermatologic, cardiovascular, gastrointestinal, and orthopedic systems. The wide range of presentations is consistent with the multiplicity of mutations observed in the causative protein. This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

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Jordyn K. Lenard, Ryan D. Adkins, OCA, Michal Harel, Jaime Prilusky