7NY7
Crystal structure of the Capsaspora owczarzaki macroH2A macrodomain in complex with ADP-ribose
Summary for 7NY7
| Entry DOI | 10.2210/pdb7ny7/pdb |
| Descriptor | Histone macroH2A1.1, 1,2-ETHANEDIOL, ADENOSINE-5-DIPHOSPHORIBOSE, ... (4 entities in total) |
| Functional Keywords | macrodomain, adp-ribose, nad+ metabolism, parp1, nuclear protein |
| Biological source | Capsaspora owczarzaki (strain ATCC 30864) |
| Total number of polymer chains | 1 |
| Total formula weight | 23752.38 |
| Authors | Guberovic, I.,Knobloch, G.,Basquin, J.,Buschbeck, M.,Ladurner, A.G. (deposition date: 2021-03-21, release date: 2021-11-24, Last modification date: 2024-01-31) |
| Primary citation | Guberovic, I.,Hurtado-Bages, S.,Rivera-Casas, C.,Knobloch, G.,Malinverni, R.,Valero, V.,Leger, M.M.,Garcia, J.,Basquin, J.,Gomez de Cedron, M.,Frigole-Vivas, M.,Cheema, M.S.,Perez, A.,Ausio, J.,Ramirez de Molina, A.,Salvatella, X.,Ruiz-Trillo, I.,Eirin-Lopez, J.M.,Ladurner, A.G.,Buschbeck, M. Evolution of a histone variant involved in compartmental regulation of NAD metabolism. Nat.Struct.Mol.Biol., 28:1009-1019, 2021 Cited by PubMed Abstract: NAD metabolism is essential for all forms of life. Compartmental regulation of NAD consumption, especially between the nucleus and the mitochondria, is required for energy homeostasis. However, how compartmental regulation evolved remains unclear. In the present study, we investigated the evolution of the macrodomain-containing histone variant macroH2A1.1, an integral chromatin component that limits nuclear NAD consumption by inhibiting poly(ADP-ribose) polymerase 1 in vertebrate cells. We found that macroH2A originated in premetazoan protists. The crystal structure of the macroH2A macrodomain from the protist Capsaspora owczarzaki allowed us to identify highly conserved principles of ligand binding and pinpoint key residue substitutions, selected for during the evolution of the vertebrate stem lineage. Metabolic characterization of the Capsaspora lifecycle suggested that the metabolic function of macroH2A was associated with nonproliferative stages. Taken together, we provide insight into the evolution of a chromatin element involved in compartmental NAD regulation, relevant for understanding its metabolism and potential therapeutic applications. PubMed: 34887560DOI: 10.1038/s41594-021-00692-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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