4BSN

Crystal structure of the Nuclear Export Receptor CRM1 (exportin-1) lacking the C-terminal helical extension at 4.1A

Summary for 4BSN

• Entry DOI: 10.2210/pdb4bsn/pdb
• Related: 4BSM
• Descriptor: EXPORTIN-1 (1 entity in total)
• Functional Keywords: protein transport, heat repeat protein, importin-beta superfamily, nucleocytoplasmic transport of protein and rnp cargoes
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: O14980
• Total number of polymer chains: 1
• Total formula weight: 118863.17

Authors

Dian, C.,Bernaudat, F.,Langer, K.,Oliva, M.F.,Fornerod, M.,Schoehn, G.,Muller, C.W.,Petosa, C. (deposition date: 2013-06-11, release date: 2013-07-31, Last modification date: 2023-12-20)

Primary citation

Dian, C.,Bernaudat, F.,Langer, K.,Oliva, M.F.,Fornerod, M.,Schoehn, G.,Muller, C.W.,Petosa, C.
Structure of a Truncation Mutant of the Nuclear Export Factor Crm1 Provides Insights Into the Auto-Inhibitory Role of its C-Terminal Helix.
Structure, 21:1338-, 2013

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.

PubMed: 23850454
DOI: 10.1016/J.STR.2013.06.003

Experimental method

X-RAY DIFFRACTION (4.1 Å)