7VPW
Crystal structure of Transportin-1 in complex with BAP1 PY-NLS (residues 706-724)
Summary for 7VPW
| Entry DOI | 10.2210/pdb7vpw/pdb |
| Descriptor | BRCA1-associated protein 1 (BAP1), Transportin-1 (2 entities in total) |
| Functional Keywords | transportin-1, brca1-associated protein 1, bap1, nuclear import, py-nls, deubiquitinase, dub, protein transport |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 100969.51 |
| Authors | Yang, T.J.,Hsu, S.T.D. (deposition date: 2021-10-18, release date: 2022-04-20, Last modification date: 2023-11-29) |
| Primary citation | Yang, T.J.,Li, T.N.,Huang, R.S.,Pan, M.Y.,Lin, S.Y.,Lin, S.,Wu, K.P.,Wang, L.H.,Hsu, S.D. Tumor suppressor BAP1 nuclear import is governed by transportin-1. J.Cell Biol., 221:-, 2022 Cited by PubMed Abstract: Subcellular localization of the deubiquitinating enzyme BAP1 is deterministic for its tumor suppressor activity. While the monoubiquitination of BAP1 by an atypical E2/E3-conjugated enzyme UBE2O and BAP1 auto-deubiquitination are known to regulate its nuclear localization, the molecular mechanism by which BAP1 is imported into the nucleus has remained elusive. Here, we demonstrated that transportin-1 (TNPO1, also known as Karyopherin β2 or Kapβ2) targets an atypical C-terminal proline-tyrosine nuclear localization signal (PY-NLS) motif of BAP1 and serves as the primary nuclear transporter of BAP1 to achieve its nuclear import. TNPO1 binding dissociates dimeric BAP1 and sequesters the monoubiquitination sites flanking the PY-NLS of BAP1 to counteract the function of UBE2O that retains BAP1 in the cytosol. Our findings shed light on how TNPO1 regulates the nuclear import, self-association, and monoubiquitination of BAP1 pertinent to oncogenesis. PubMed: 35446349DOI: 10.1083/jcb.202201094 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.76 Å) |
Structure validation
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