|Title||Structural Characterization of the DAXX N-Terminal Helical Bundle Domain and Its Complex with Rassf1C|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Escobar-Cabrera, E, Lau, DKW, Giovinazzi, S, Ishov, AM, McIntosh, LP|
|Date Published||DEC 8|
DAXX is a scaffold protein with diverse roles including transcription and cell cycle regulation. Using NMR spectroscopy, we demonstrate that the C-terminal half of DAXX is intrinsically disordered, whereas a folded domain is present near its N terminus. This domain forms a left-handed four-helix bundle (H1, H2, H4, H5). However, due to a crossover helix (H3), this topology differs from that of the Sin3 PAH domain, which to date has been used as a model for DAXX. The N-terminal residues of the tumor suppressor Rassf1C fold into an amphipathic alpha helix upon binding this DAXX domain via a shallow cleft along the flexible helices H2 and H5 (K(D) similar to 60 mu M). Based on a proposed DAXX recognition motif as hydrophobic residues preceded by negatively charged groups, we found that peptide models of p53 and Mdm2 also bound the helical bundle. These data provide a structural foundation for understanding the diverse functions of DAXX.