Extended Data Fig. 4: Model of BRAF-KD:MEK:14-3-3 hexamer and unambiguous electron density of pS729 in BRAF bound to 14-3-3.
From: Negative regulation of RAF kinase activity by ATP is overcome by 14-3-3-induced dimerization
a, Model of hetero-hexamer formed by MEK1 (red, salmon), BRAF (blue, marine) and 14-3-3 (orange, yellow). Compared to the BRAF/14-3-3 crystal structure (Fig. 2c), the BRAF dimer must undock from the α9 helix of one 14-3-3 protomer to bind MEK1 (as observed by SEC in Fig. 2a). Undocking is easily feasible (inset) while maintaining pS729 binding (peptide shown in pink) to 14-3-3. b, Detailed view of one BRAF-pSer729 (blue) – 14-3-3 (orange) interaction. Electron density map is 2Fo – Fc contoured to 2.0σ.
