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TitleStructural basis for a nucleoporin exportin complex between RanBP2, SUMO1-RanGAP1, the E2 Ubc9, Crm1 and the Ran GTPase.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 6403, Year 2025
Publish dateJul 11, 2025
AuthorsVladimir Baytshtok / Michael A DiMattia / Christopher D Lima /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:40640138 / PubMed Central
MethodsEM (single particle)
Resolution2.89 - 3.52 Å
Structure data

EMDB-44235, PDB-9b62:
Human RANBP2/RAN(GTP)/RANGAP1-SUMO1/UBC9/CRM1/RAN(GTP) - composite map and model
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-44236: Human RANBP2/SUMO1-RANGAP1/RAN(GTP)/UBC9/CRM1/RAN(GTP) complex - overall map
Method: EM (single particle) / Resolution: 3.17 Å

EMDB-44237: Focused refinement map on CRM1/RAN(GTP) from human RANBP2/RAN(GTP)/SUMO1-RANGAP1/UBC9/CRM1/RAN(GTP) complex
Method: EM (single particle) / Resolution: 2.89 Å

EMDB-44238: Overall map for the RANBP2 RBD4/RAN(GTP)/RANGAP1 GAP domain from human RANBP2/RAN(GTP)/SUMO1-RANGAP1/UBC9/CRM1/RAN(GTP) complex
Method: EM (single particle) / Resolution: 3.52 Å

EMDB-44239: Focused refinement map on RANBP2 RBD4/RAN(GTP) from human RANBP2/RAN(GTP)/SUMO1-RANGAP1/UBC9/CRM1/RAN(GTP) complex
Method: EM (single particle) / Resolution: 3.52 Å

EMDB-44240: Focused refinement map on RANGAP1 GAP domain from human RANBP2/RAN(GTP)/SUMO1-RANGAP1/UBC9/CRM1/RAN(GTP) complex
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-44241: Overall map for human RANBP2/RAN(GTP)/SUMO1-RANGAP1/UBC9/CRM1/RAN(GTP) complex where SUMO1-RANGAP1/UBC9 was present
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-44242: Focused refinement map on RanGAP1 C-terminal domain-SUMO1/UBC9/RANBP2 E3 domain for human RANBP2/RAN(GTP)/SUMO1-RANGAP1/UBC9/CRM1/RAN(GTP) complex where SUMO1-RANGAP1/UBC9 was present
Method: EM (single particle) / Resolution: 3.29 Å

EMDB-44243: Focused refinement map for RanGAP1 C-terminal domain-SUMO1/UBC9/RANBP2/CRM1/RAN(GTP) for human RANBP2/RAN(GTP)/SUMO1-RANGAP1/UBC9/CRM1/RAN(GTP) complex where SUMO1-RANGAP1/UBC9 was present
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / karyopherin / SUMO E3 / SUMO E2 / transporter / GTPase / GTPase activating protein / exportin / G-protein

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