Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes.

ABSTRACT: RAF family kinases are RAS-activated switches that initiate signalling through the MAP kinase cascade to control cellular proliferation, differentiation and survival^1-3. RAF activity is tightly regulated and inappropriate activation is a frequent cause of cancer^4-6; however, the structural basis for RAF regulation is poorly understood at present. Here we use cryo-electron microscopy to determine autoinhibited and active-state structures of full-length BRAF in complexes with MEK1 and a 14-3-3 dimer. The reconstruction reveals an inactive BRAF-MEK1 complex restrained in a cradle formed by the 14-3-3 dimer, which binds the phosphorylated S365 and S729 sites that flank the BRAF kinase domain. The BRAF cysteine-rich domain occupies a central position that stabilizes this a

SUBMITTER: Park E 

PROVIDER: S-EPMC7014971 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature