Multipurpose MRG Domain Involved in Cell Senescence and Proliferation Exhibits Structural Homology to a DNA-Interacting Domain
| Autor: | Bhakti M. Kirtane, Florante A. Quiocho, Carmen M. Moure, Olivia M. Pereira-Smith, Robert L. Welschhans, Brian R. Bowman, Kaoru Tominaga |
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| Rok vydání: | 2006 |
| Předmět: |
Molecular Sequence Data
Biology Crystallography X-Ray DNA-binding protein Homology (biology) Evolution Molecular 03 medical and health sciences 0302 clinical medicine Structural Biology Protein Interaction Mapping Recombinase Humans Amino Acid Sequence Tyrosine Nuclear protein Molecular Biology Cellular Senescence Cell Proliferation Histone Acetyltransferases 030304 developmental biology Genetics 0303 health sciences Binding Sites Binding protein Intracellular Signaling Peptides and Proteins Nuclear Proteins Protein Structure Tertiary Cell biology Integrase DNA-Binding Proteins Structural Homology Protein 030220 oncology & carcinogenesis Mutagenesis Site-Directed biology.protein Histone deacetylase Carrier Proteins Transcription Factors |
| Zdroj: | Structure. 14:151-158 |
| ISSN: | 0969-2126 |
| Popis: | The ubiquitous MRG/MORF family of proteins is involved in cell senescence, or the terminal loss of proliferative potential, a model for aging and tumor suppression at the cellular level. These proteins are defined by the approximately 20 kDa MRG domain that binds a plethora of transcriptional regulators and chromatin-remodeling factors, including the histone deacetylase transcriptional corepressor mSin3A and the novel nuclear protein PAM14, and they are also known components of the Tip60/NuA4 complex via interactions with the MRG binding protein (MRGBP). We present here the crystal structure of a prototypic MRG domain from human MRG15 whose core consists of two orthogonal helix hairpins. Despite the lack of sequence similarity, the core structure has surprisingly striking homology to a DNA-interacting domain of the tyrosine site-specific recombinases XerD, lambda integrase, and Cre. Site-directed mutagenesis studies based on the X-ray structure and bioinformatics identified key residues involved in the binding of PAM14 and MRGBP. |
| Databáze: | OpenAIRE |
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