4BSM

Crystal structure of the Nuclear Export Receptor CRM1 (exportin-1) lacking the C-terminal helical extension at 4.5A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.50 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.233 

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This is version 1.2 of the entry. See complete history


Literature

Structure of a Truncation Mutant of the Nuclear Export Factor Crm1 Provides Insights Into the Auto-Inhibitory Role of its C-Terminal Helix.

Dian, C.Bernaudat, F.Langer, K.Oliva, M.F.Fornerod, M.Schoehn, G.Muller, C.W.Petosa, C.

(2013) Structure 21: 1338

  • DOI: https://doi.org/10.1016/j.str.2013.06.003
  • Primary Citation of Related Structures:  
    4BSM, 4BSN

  • PubMed 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.


  • Organizational Affiliation

    Université de Grenoble Alpes, Institut de Biologie Structurale, 38027 Grenoble, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
EXPORTIN-11,032Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O14980 (Homo sapiens)
Explore O14980 
Go to UniProtKB:  O14980
PHAROS:  O14980
GTEx:  ENSG00000082898 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14980
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.50 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.233 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 148.64α = 90
b = 248.33β = 90
c = 107.2γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-07-31
    Type: Initial release
  • Version 1.1: 2013-08-28
    Changes: Database references
  • Version 1.2: 2023-12-20
    Changes: Data collection, Database references, Other, Refinement description