Structural basis for a nucleoporin exportin complex between RanBP2, SUMO1-RanGAP1, the E2 Ubc9, Crm1 and the Ran GTPase Journal Article
| Authors: | Baytshtok, V.; DiMattia, M. A.; Lima, C. D. |
| Article Title: | Structural basis for a nucleoporin exportin complex between RanBP2, SUMO1-RanGAP1, the E2 Ubc9, Crm1 and the Ran GTPase |
| Abstract: | The human nucleoporin RanBP2/Nup358 interacts with SUMO1-modified RanGAP1 and the SUMO E2 Ubc9 at the nuclear pore complex (NPC) to promote export and disassembly of exportin Crm1/Ran(GTP)/cargo complexes. In mitosis, RanBP2/SUMO1-RanGAP1/Ubc9 remains intact after NPC disassembly and is recruited to kinetochores and mitotic spindles by Crm1 where it contributes to mitotic progression. RanBP2 binds SUMO1-RanGAP1/Ubc9 via motifs that also catalyze SUMO E3 ligase activity. Here, we resolve cryo-EM structures of a RanBP2 C-terminal fragment in complex with Crm1, SUMO1-RanGAP1/Ubc9, and two molecules of Ran(GTP). These structures reveal several interactions with Crm1 including a nuclear export signal (NES) for RanGAP1, the deletion of which mislocalizes RanGAP1 and the Ran GTPase in cells. Our structural and biochemical results support models in which RanBP2 E3 ligase activity is dependent on Crm1, the RanGAP1 NES and Ran GTPase cycling. © The Author(s) 2025. |
| Keywords: | protein expression; genetics; nonhuman; polymerase chain reaction; protein localization; mitosis; metabolism; protein; protein binding; protein interaction; enzyme activity; hela cells; molecular cloning; chemistry; protein purification; escherichia coli; molecular analysis; guanosine triphosphatase activating protein; mitosis spindle; gtpase-activating proteins; models, molecular; protein structure; sumo-1 protein; ubiquitin-conjugating enzymes; ultrastructure; molecular model; protein modification; expression vector; ubiquitin conjugating enzyme; receptors, cytoplasmic and nuclear; nuclear pore complex proteins; chaperone; cryoelectron microscopy; guanosine triphosphatase; exportin 1; karyopherins; cross linking; sumo 1 protein; molecular chaperones; cell receptor; exportin 5; nuclear pore; nucleoporin; nuclear pore complex; dna library; ubiquitin-conjugating enzyme ubc9; ran gtp-binding protein; ran protein; kinetochore; ran-binding protein 2; rangap1 protein, human; nuclear export signal; cell component; humans; human; article; karyopherin; hela cell line; baculoviral iap repeat containing protein 5; exportin 1 protein; sumo conjugating enzyme ubc9; ran protein, human; sumo1 protein, human |
| Journal Title: | Nature Communications |
| Volume: | 16 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-07-11 |
| Start Page: | 6403 |
| Language: | English |
| DOI: | 10.1038/s41467-025-61694-1 |
| PUBMED: | 40640138 |
| PROVIDER: | scopus |
| PMCID: | PMC12246119 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Christopher D. Lima -- Source: Scopus |
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