4BSM: Crystal Structure Of The Nuclear Export Receptor Crm1 (exportin-1) Lacking The C-terminal Helical Extension At 4.5a

Citation:
Abstract
Chromosome region maintenance 1/exportin1/Xpo1 (CRM1) associates with the GTPase Ran to mediate the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES). CRM1 consists of helical hairpin HEAT repeats and a C-terminal helical extension (C-extension) that inhibits the binding of NES-bearing cargos. We report the crystal structure and small-angle X-ray scattering analysis of a human CRM1 mutant with enhanced NES-binding activity due to deletion of the C-extension. We show that loss of the C-extension leads to a repositioning of CRM1's C-terminal repeats and to a more extended overall conformation. Normal mode analysis predicts reduced rigidity for the deletion mutant, consistent with an observed decrease in thermal stability. Point mutations that destabilize the C-extension shift CRM1 to the more extended conformation, reduce thermal stability, and enhance NES-binding activity. These findings suggest that an important mechanism by which the C-extension regulates CRM1's cargo-binding affinity is by modulating the conformation and flexibility of its HEAT repeats.
PDB ID: 4BSMDownload
MMDB ID: 112179
PDB Deposition Date: 2013/6/10
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 4.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4BSM: monomeric; determined by author and by software (PISA)
Molecular Components in 4BSM
Label Count Molecule
Protein (1 molecule)
1
Exportin-1(Gene symbol: XPO1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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