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

Publication date: Available online 1 February 2018 Source:Journal of Structural Biology Author(s): Alice Ballone, Federica Centorrino, Madita Wolter, Christian Ottmann 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.

Source: Journal of Structural Biology - March 9, 2018 Category: Biology Source Type: research