Intrinsic structural disorder of the C-terminal activation domain from thebZIP transcription factor Fos

The bZIP proto-oncoprotein c-Fos activates transcription of a wide variety of genes involved in cell growth. The C-terminal activation domain of c-Fos is functionally independent of the remainder of the protein. Fos-AD corres ponds to the C-terminal activation domain of human c-Fos (residues 216-380) . Foe-AD suppresses (squelches) transcription in vitro, as expected for a f unctional activation domain lacking a DNA-binding domain. Fos-AD is unstruc tured and highly mobile, as demonstrated by circular dichroism spectra indi cative of unfolded proteins, a lack of H-1 chemical shift dispersion, and n egative H-1-N-15 heteronuclear nuclear Overhauser effects. The hydrodynamic properties of Fos-AD are also consistent with an extended structure. We co nclude that the C-terminal domain of human c-Fos is biologically active yet intrinsically disordered. Our results suggest that conformational disorder is an integral aspect of the diverse contributions to transcriptional regu lation by c-Fos.