3M1I: Crystal Structure of Yeast Crm1 (Xpo1p) in Complex With Yeast Ranbp1 (Yrb1p) and Yeast Rangtp (Gsp1pgtp)

The karyopherin CRM1 mediates nuclear export of proteins and ribonucleoproteins bearing a leucine-rich nuclear export signal (NES). To elucidate the precise mechanism by which NES-cargos are dissociated from CRM1 in the cytoplasm, which is important for transport directionality, we determined a 2.0-A resolution crystal structure of yeast CRM1:RanBP1:RanGTP complex, an intermediate in the disassembly of the CRM1 nuclear export complex. The structure shows that on association of Ran-binding domain (RanBD) of RanBP1 with CRM1:NES-cargo:RanGTP complex, RanBD and the C-terminal acidic tail of Ran induce a large movement of the intra-HEAT9 loop of CRM1. The loop moves to the CRM1 inner surface immediately behind the NES-binding site and causes conformational rearrangements in HEAT repeats 11 and 12 so that the hydrophobic NES-binding cleft on the CRM1 outer surface closes, squeezing out the NES-cargo. This allosteric mechanism accelerates dissociation of NES by over two orders of magnitude. Structure-based mutagenesis indicated that the HEAT9 loop also functions as an allosteric autoinhibitor to stabilize CRM1 in a conformation that is unable to bind NES-cargo in the absence of RanGTP.
PDB ID: 3M1IDownload
MMDB ID: 82493
PDB Deposition Date: 2010/3/5
Updated in MMDB: 2010/06 
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 3M1I: trimeric; determined by author and by software (PISA)
Molecular Components in 3M1I
Label Count Molecule
Proteins (3 molecules)
Gtp-binding Nuclear Protein Gsp1/cnr1
Molecule annotation
Ran-specific Gtpase-activating Protein 1
Molecule annotation
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB