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Structural basis for a nucleoporin exportin complex between RanBP2, SUMO1-RanGAP1, the E2 Ubc9, Crm1 and the Ran GTPase
Open accessPreprint — published as 10.1038/s41467-025-61694-1 · Paper page
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. Interestingly, 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 unanticipated 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.
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Metadata
- Authors
- Baytshtok, V., DiMattia, M. A., & Lima, C. D.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Lima, Christopher D.
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2024-10-05
- Volume
- 16
- Issue
- 1
- Pages
- 6403-6403
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12246119
- OpenAlex
- W4412181755
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 9 · 2025: 2
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- U.S. Department of Health and Human Services (P30 CA008748, R35 GM118080)
- National Institutes of Health (CA008748)
- National Cancer Institute (CA008748, P30CA008748)
- National Institute of General Medical Sciences (R35GM118080)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- RanBP2, Nup358, SUMO1, RanGAP1, Ubc9, CRM1, Ran GTPase, nuclear pore complex, SUMOylation, SUMO E3 ligase, nuclear export signal, mitosis, kinetochore, protein complex structure
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