Conformational Activation of Poly(ADP-ribose) Polymerase-1 upon DNA Binding Revealed by Small-Angle X-ray Scattering
| Autor: | Meilan Wu, Peng Gao, Zhihua Tao, Hung-wen Liu, Steven O. Mansoorabadi, Liang Guo, Sai Venkatesh Pingali |
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| Rok vydání: | 2014 |
| Předmět: |
HMG-box
Protein Conformation DNA damage DNA repair Poly ADP ribose polymerase Poly (ADP-Ribose) Polymerase-1 DNA DNA-binding domain Biology Ligand (biochemistry) Biochemistry Article Crystallography chemistry.chemical_compound X-Ray Diffraction chemistry Scattering Small Angle Biophysics Humans Poly(ADP-ribose) Polymerases Protein Binding Binding domain |
| Zdroj: | Biochemistry |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that plays key roles in several fundamental cellular processes. PARP-1 catalyzes the polymerization of nicotinamide adenine dinucleotide on itself and other acceptor proteins, forming long branched poly(ADP-ribose) polymers. The catalytic activity of PARP-1 is stimulated upon binding to damaged DNA, but how this signal is transmitted from the N-terminal DNA binding domain to the C-terminal catalytic domain in the context of the full-length enzyme is unknown. In this paper, small-angle X-ray scattering experiments and molecular dynamics simulations were used to gain insight into the conformational changes that occur during the catalytic activation of PARP-1 by an 8-mer DNA ligand. The data are consistent with a model in which binding of the DNA ligand establishes interdomain interactions between the DNA binding and catalytic domains, which induces an allosteric change in the active site that promotes catalysis. Moreover, the PARP-1-8-mer complex is seen to adopt a conformation that is poised to recruit DNA repair factors to the site of DNA damage. This study provides the first structural information about the DNA-induced conformational activation of full-length PARP-1. |
| Databáze: | OpenAIRE |
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