2. Academic Validation
  3. The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes

The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes

  • Nat Commun. 2016 May 10;7:11482. doi: 10.1038/ncomms11482.
Tobias Ritterhoff 1 2,  Hrishikesh Das 1 3,  Götz Hofhaus 3,  Rasmus R Schröder 3,  Annette Flotho 1,  Frauke Melchior 1
Affiliations

Affiliations

  • 1 Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg 69120, Germany.
  • 2 Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
  • 3 Cryo Electron Microscopy, CellNetworks, BioQuant, Universitätsklinikum Heidelberg, Heidelberg 69120, Germany.
PMID: 27160050 DOI: 10.1038/ncomms11482
Abstract

Continuous cycles of nucleocytoplasmic transport require disassembly of transport receptor/Ran-GTP complexes in the cytoplasm. A basic disassembly mechanism in all eukaryotes depends on soluble RanGAP and RanBP1. In vertebrates, a significant fraction of RanGAP1 stably interacts with the nucleoporin RanBP2 at a binding site that is flanked by FG-repeats and Ran-binding domains, and overlaps with RanBP2's SUMO E3 ligase region. Here, we show that the RanBP2/RanGAP1*SUMO1/Ubc9 complex functions as an autonomous disassembly machine with a preference for the export receptor CRM1. We describe three in vitro reconstituted disassembly intermediates, which show binding of a CRM1 export complex via two FG-repeat patches, cargo-release by RanBP2's Ran-binding domains and retention of free CRM1 at RanBP2 after Ran-GTP hydrolysis. Intriguingly, all intermediates are compatible with SUMO E3 ligase activity, suggesting that the RanBP2/RanGAP1*SUMO1/Ubc9 complex may link Crm1- and SUMO-dependent functions.

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