Structural Evidence for Feedback Activation by Ras·GTP of the Ras-Specific Nucleotide Exchange Factor SOS
| Autor: | Dafna Bar-Sagi, Brian E. Hall, S. Mariana Margarit, Michelle Pirruccello, Holger Sondermann, John Kuriyan, Bhushan Nagar, André Hoelz |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
GTP'
Son of Sevenless General Biochemistry Genetics and Molecular Biology Nucleotide exchange factor Phosphatidylinositol 3-Kinases Growth factor receptor Catalytic Domain Humans Binding site Feedback Physiological biology Molecular Structure Sequence Homology Amino Acid Nucleotides Biochemistry Genetics and Molecular Biology(all) Cell Membrane Active site biochemical phenomena metabolism and nutrition Cell biology Protein Structure Tertiary enzymes and coenzymes (carbohydrates) Eukaryotic Cells Biochemistry Son of Sevenless Proteins SOS1 biology.protein ras Proteins bacteria Guanosine Triphosphate SOS1 Protein Protein Binding |
| Zdroj: | Cell. 112(5):685-695 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/s0092-8674(03)00149-1 |
| Popis: | Growth factor receptors activate Ras by recruiting the nucleotide exchange factor son of sevenless (SOS) to the cell membrane, thereby triggering the production of GTP-loaded Ras. Crystallographic analyses of Ras bound to the catalytic module of SOS have led to the unexpected discovery of a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras·GTP. The crystal structures suggest that Ras·GTP stabilizes the active site of SOS allosterically, and we show that Ras·GTP forms ternary complexes with SOS cat in solution and increases significantly the rate of SOS cat -stimulated nucleotide release from Ras. These results demonstrate the existence of a positive feedback mechanism for the spatial and temporal regulation of Ras. |
| Databáze: | OpenAIRE |
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