Abstract
The deviant Ras activation machinery is found in approximately 30% of all human cancers. SOS1 is an important protagonist of this pathway that plays a key-role in aberrant cell proliferation and differentiation. Interaction of SOS1 with 14-3-3 proteins modulates SOS1 activity in Ras-MAPK signaling. In the present study, we analyze the 14-3-3/SOS1 protein-protein interaction (PPI) by different biochemical assays and report the high resolution crystal structure of a 13-mer motif of SOS1 bound to 14-3-3ζ. These structural and functional insights are important for the evaluation of this PPI interface for small-molecule stabilization as a new starting point for modulating the Ras-Raf-MAPK pathway.
Original language | English |
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Pages (from-to) | 210-215 |
Number of pages | 6 |
Journal | Journal of Structural Biology |
Volume | 202 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Jun 2018 |
Keywords
- Differential scanning fluorimetry
- Fluorescence polarization
- Isothermal titration calorimetry
- Son of sevenless homolog 1
- X-ray crystallography
- Phosphorylation
- Multiprotein Complexes/chemistry
- Humans
- SOS1 Protein/chemistry
- Protein Binding
- 14-3-3 Proteins/chemistry
- Cell Proliferation/genetics
- Mutation
- Protein Interaction Maps/genetics