Nuclear export mediated by CRM1: from X-ray structures to mechanism in living cells

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Nucleocytoplasmic transport of macromolecues is a fundamental activity essential for a plethora of physiological functions of eukaryotic cells. CRM1 is a major nuclear export receptor (exportin) that mediates nuclear export of cargo macromolecules bearing a leucine-rich nuclear export signal (NES). In the nucleus, CRM1 binds cooperatively to RanGTP and NES-cargo, forming a trimeric complex. In this study, we determined X-ray crystal structure of unliganded Saccharomyces cerevisiaeCRM1 at 2.1-Åresolution. Comparison with the structure of CRM1-NES-RanGTP complex and structure-based mutational analyses revealed the mechanism of autoinhibition of CRM1 and the mechanism by which the binding of NES to CRM1 depends on RanGTP.