Shape of the transcription factor c-Fos in solution and in a lipid environment studied by Small Angle X-ray Scattering

Campinas

Otro; Laboratorio Nacional de Luz Sincrotron; 2005

Laboratorio Nacional de Luz Sincrotron

c-Fos, the protein product of the gene c-fos, appears veryrapidly upon stimulus to promote expression of target genesas a transcription factor. c-Fos heterodimerizes with c-Jun, anothertranscription factor, to form the complex AP-1 that bindsto specific target DNA. Both proteins are involved in manynormal (proliferation, differentiation and apoptosis) and abnormal(oncogenic) cellular processes [1][2]. Although theyare considered as soluble, their amphitropic features suggestthat they may aggregate in solution [3][4]. Their structure hasbeen elucidated by crystallography only for the portions responsiblefor their respective basic DNA binding domain andthe dimerization leucine zipper domain, which adopt alpha helixstructure when stabilized by DNA [5]. However, their generalconformation in solution is that of intrinsically unfoldedproteins [6]. We have characterized by SAXS the molecularconformation of c-Fos and c-Jun, and their interactions in solution.