Structural Characterization of the DAXX N-Terminal Helical Bundle Domain and Its Complex with Rassf1C
| Autor: | Serena Giovinazzi, Eric Escobar-Cabrera, Lawrence P. McIntosh, Desmond K. W. Lau, Alexander M. Ishov |
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| Jazyk: | angličtina |
| Předmět: |
Models
Molecular Scaffold protein Magnetic Resonance Spectroscopy Peptide Protein Structure Secondary 03 medical and health sciences 0302 clinical medicine Death-associated protein 6 Sequence Analysis Protein Structural Biology Transcription (biology) Protein Interaction Mapping Humans Protein Interaction Domains and Motifs Molecular Biology Adaptor Proteins Signal Transducing Sequence Deletion 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites biology Tumor Suppressor Proteins Nuclear Proteins Nuclear magnetic resonance spectroscopy Protein Structure Tertiary N-terminus Crystallography chemistry Multiprotein Complexes 030220 oncology & carcinogenesis Helix biology.protein Biophysics Mdm2 Mutant Proteins Co-Repressor Proteins Hydrophobic and Hydrophilic Interactions Molecular Chaperones |
| Zdroj: | Structure. (12):1642-1653 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2010.09.016 |
| Popis: | Summary 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 α helix upon binding this DAXX domain via a shallow cleft along the flexible helices H2 and H5 (K D ∼60 μM). 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. |
| Databáze: | OpenAIRE |
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