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PDBsum entry 4bsm
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Protein transport
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PDB id
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4bsm
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References listed in PDB file
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Key reference
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Title
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Structure of a truncation mutant of the nuclear export factor crm1 provides insights into the auto-Inhibitory role of its c-Terminal helix.
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Authors
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C.Dian,
F.Bernaudat,
K.Langer,
M.F.Oliva,
M.Fornerod,
G.Schoehn,
C.W.Müller,
C.Petosa.
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Ref.
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Structure, 2013,
21,
1338-1349.
[DOI no: ]
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PubMed id
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Abstract
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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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