Summary for 4MZ5
| Entry DOI | 10.2210/pdb4mz5/pdb |
| Related | 1ELJ 3UKW 4MZ6 |
| Descriptor | Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial, Importin subunit alpha-1 (3 entities in total) |
| Functional Keywords | arm repeat, protein transport, importin, nucleus |
| Biological source | Mus musculus (mouse) More |
| Cellular location | Cytoplasm (By similarity): P33316 Isoform 2: Nucleus. Isoform 3: Mitochondrion: P52293 |
| Total number of polymer chains | 3 |
| Total formula weight | 57890.51 |
| Authors | Marfori, M.,Rona, G.,Vertessy, B.G.,Kobe, B. (deposition date: 2013-09-29, release date: 2013-11-13, Last modification date: 2024-02-28) |
| Primary citation | Rona, G.,Marfori, M.,Borsos, M.,Scheer, I.,Takacs, E.,Toth, J.,Babos, F.,Magyar, A.,Erdei, A.,Bozoky, Z.,Buday, L.,Kobe, B.,Vertessy, B.G. Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: structural and mechanistic insights. Acta Crystallogr.,Sect.D, 69:2495-2505, 2013 Cited by PubMed Abstract: Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in the regulation of nucleocytoplasmic transport. The nuclear isoform of human dUTPase, an enzyme that is essential for genomic integrity, has been shown to be phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear localization signal; however, the effect of this phosphorylation is not yet known. To investigate this issue, an integrated set of structural, molecular and cell biological methods were employed. It is shown that NLS-adjacent phosphorylation of dUTPase occurs during the M phase of the cell cycle. Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus. Isothermal titration microcalorimetry and additional independent biophysical techniques show that the interaction between dUTPase and importin-α, the karyopherin molecule responsible for `classical' NLS binding, is weakened significantly in the case of the S11E hyperphosphorylation-mimicking mutant. The structures of the importin-α-wild-type and the importin-α-hyperphosphorylation-mimicking dUTPase NLS complexes provide structural insights into the molecular details of this regulation. The data indicate that the post-translational modification of dUTPase during the cell cycle may modulate the nuclear availability of this enzyme. PubMed: 24311590DOI: 10.1107/S0907444913023354 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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