Structural characterization of 14-3-3ζ in complex with the human Son of sevenless homolog 1 (SOS1)

Alice Ballone, Federica Centorrino, Madita Wolter, Christian Ottmann

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14 Citations (Scopus)
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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 languageEnglish
Pages (from-to)210-215
Number of pages6
JournalJournal of Structural Biology
Issue number3
Publication statusPublished - 1 Jun 2018


  • 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


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