Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex.

Article Details

Citation

Petosa C, Schoehn G, Askjaer P, Bauer U, Moulin M, Steuerwald U, Soler-Lopez M, Baudin F, Mattaj IW, Muller CW

Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex.

Mol Cell. 2004 Dec 3;16(5):761-75.

PubMed ID
15574331 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
GTP-binding nuclear protein RanP62826Details
Exportin-1O14980Details