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Structural characterization of 14-3-3ζ in complex with the human Son of sevenless homolog 1 (SOS1).
J Struct Biol
; 202(3): 210-215, 2018 06.
Article
in English
| MEDLINE
| ID: mdl-29408703
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.