Structure of a truncation mutant of the nuclear export factor CRM1 provides insights into the auto-inhibitory role of its C-terminal helix. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Structure (London, England : 1993) Année : 2013

Structure of a truncation mutant of the nuclear export factor CRM1 provides insights into the auto-inhibitory role of its C-terminal helix.

Cyril Dian
Karla Langer
  • Fonction : Auteur
Mizar Francesca Oliva
  • Fonction : Auteur
  • PersonId : 785775
  • IdRef : 223499064
Maarten Fornerod
  • Fonction : Auteur
Guy Schoehn
Christoph W Müller
  • Fonction : Auteur
Carlo Petosa

Résumé

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.
Fichier non déposé

Dates et versions

hal-01322366 , version 1 (27-05-2016)

Identifiants

  • HAL Id : hal-01322366 , version 1
  • PUBMED : 23850454

Citer

Cyril Dian, Florent Bernaudat, Karla Langer, Mizar Francesca Oliva, Maarten Fornerod, et al.. Structure of a truncation mutant of the nuclear export factor CRM1 provides insights into the auto-inhibitory role of its C-terminal helix.. Structure (London, England : 1993), 2013, 21 (8), pp.1338-49. ⟨hal-01322366⟩
257 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More