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

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.
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Structure (London, England : 1993), 2013, 21 (8), pp.1338-49
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http://hal.univ-grenoble-alpes.fr/hal-01322366
Contributeur : Frank Thomas <>
Soumis le : vendredi 27 mai 2016 - 10:00:45
Dernière modification le : jeudi 11 janvier 2018 - 06:15:24

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

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Cyril Dian, Florent Bernaudat, Karla Langer, Mizar F 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〉

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