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-Structure paper
タイトル | Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex. |
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ジャーナル・号・ページ | Mol Cell, Vol. 16, Issue 5, Page 761-775, Year 2004 |
掲載日 | 2004年12月3日 |
![]() | Carlo Petosa / Guy Schoehn / Peter Askjaer / Ulrike Bauer / Martine Moulin / Ulrich Steuerwald / Montserrat Soler-López / Florence Baudin / Iain W Mattaj / Christoph W Müller / ![]() |
PubMed 要旨 | CRM1/Exportin1 mediates the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES) by forming a cooperative ternary complex with the NES-bearing substrate and the small GTPase ...CRM1/Exportin1 mediates the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES) by forming a cooperative ternary complex with the NES-bearing substrate and the small GTPase Ran. We present a structural model of human CRM1 based on a combination of X-ray crystallography, homology modeling, and electron microscopy. The architecture of CRM1 resembles that of the import receptor transportin1, with 19 HEAT repeats and a large loop implicated in Ran binding. Residues critical for NES recognition are identified adjacent to the cysteine residue targeted by leptomycin B (LMB), a specific CRM1 inhibitor. We present evidence that a conformational change of the Ran binding loop accounts for the cooperativity of Ran- and substrate binding and for the selective enhancement of CRM1-mediated export by the cofactor RanBP3. Our findings indicate that a single architectural and mechanistic framework can explain the divergent effects of RanGTP on substrate binding by many import and export receptors. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 2.3 - 22.0 Å |
構造データ | ![]() EMDB-1099: ![]() PDB-1w9c: |
化合物 | ![]() ChemComp-HOH: |
由来 |
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![]() | NUCLEAR PROTEIN / EXPORTIN 1 / NUCLEAR EXPORT COMPLEX |