1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

Correspondence to: Murray Stewart Email: ms@mrc-lmb.cam.ac.uk
Atomic coordinates and structure factors have been deposited in the Protein Data Bank under accession codes 1WA5 and rlwa5sf.ent, respectively.

Abstract

The nuclear import and export of macromolecular cargoes through nuclear pore complexes is mediated primarily by carriers such as importin-. Importins carry cargoes into the nucleus, whereas exportins carry cargoes to the cytoplasm. Transport is orchestrated by nuclear RanGTP, which dissociates cargoes from importins, but conversely is required for cargo binding to exportins. Here we present the 2.0 Å crystal structure of the nuclear export complex formed by exportin Cse1p complexed with its cargo (Kap60p) and RanGTP, thereby providing a structural framework for understanding nuclear protein export and the different functions of RanGTP in export and import. In the complex, Cse1p coils around both RanGTP and Kap60p, stabilizing the RanGTP-state and clamping the Kap60p importin--binding domain, ensuring that only cargo-free Kap60p is exported. Mutagenesis indicated that conformational changes in exportins couple cargo binding to high affinity for RanGTP, generating a spring-loaded molecule to facilitate disassembly of the export complex following GTP hydrolysis in the cytoplasm.

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