title: Structure of Importin13-Ubc9 complex: nuclear import and release of a key regulator of sumoylation.
abstract: Importin13 (Imp13) is an unusual β-karyopherin that is able to both import and export cargoes in and out of the nucleus. In the cytoplasm, Imp13 associates with different cargoes such as Mago-Y14 and Ubc9, and facilitates their import into the nucleus where RanGTP binding promotes the release of the cargo. In this study, we present the 2.8 Å resolution crystal structure of Imp13 in complex with the SUMO E2-conjugating enzyme, Ubc9. The structure shows an uncommon mode of cargo-karyopherin recognition with Ubc9 binding at the N-terminal portion of Imp13, occupying the entire RanGTP-binding site. Comparison of the Imp13-Ubc9 complex with Imp13-Mago-Y14 shows the remarkable plasticity of Imp13, whose conformation changes from a closed ring to an open superhelix when bound to the two different cargoes. The structure also shows that the binding mode is compatible with the sumoylated states of Ubc9. Indeed, we find that Imp13 is able to bind sumoylated Ubc9 in vitro and suppresses autosumoylation activity in the complex.
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Grünwald
authors.forename: Fulvia
authors.initials: F
authors.lastname: Bono
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D003461:Crystallography; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000235:genetics / Q000648:ultrastructure*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: C527880:IPO13 protein, human; D028884:Karyopherins; D046912:Multiprotein Complexes; C406243:RBM8A protein, human; D016601:RNA-Binding Proteins; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9