Structural basis for a nucleoporin exportin complex between RanBP2, SUMO1-RanGAP1, the E2 Ubc9, Crm1 and the Ran
Vladimir Baytshtok1,2, Michael A DiMattia1,3,2, Christopher D Lima1,4
1Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
Biorxiv : the Preprint Server for Biology
|January 7, 2025
Summary
RanBP2, a key protein in nuclear transport, interacts with SUMO1-modified RanGAP1 and Ubc9. New structures reveal how RanBP2 facilitates nuclear export and mitotic progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Structural Biology
Background:
- RanBP2/Nup358 is a nucleoporin crucial for nuclear pore complex (NPC) function and nuclear transport.
- It interacts with SUMO1-modified RanGAP1 and Ubc9, playing roles in exportin Crm1 complex disassembly and mitotic progression.
Purpose of the Study:
- To elucidate the structural basis of RanBP2 interactions with Crm1, SUMO1-RanGAP1/Ubc9, and Ran(GTP).
- To understand the mechanism of RanBP2's SUMO E3 ligase activity and its role in nuclear export and mitosis.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine high-resolution structures.
- Biochemical assays to validate structural findings and functional interactions.
Main Results:
- Cryo-EM structures reveal RanBP2 in complex with Crm1, SUMO1-RanGAP1/Ubc9, and Ran(GTP).
- Identified a novel nuclear export signal (NES) for RanGAP1 within the RanBP2 complex.
- Deletion of the RanGAP1 NES causes mislocalization of RanGAP1 and Ran GTPase.
Conclusions:
- RanBP2's SUMO E3 ligase activity is regulated by Crm1, the RanGAP1 NES, and Ran GTPase cycling.
- These interactions are critical for efficient nuclear export and proper mitotic progression.
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