Crystal Structure of the Nuclear Export Receptor CRM1 in Complex with Snurportin1 and RanGTP
Thomas Monecke,1,*
Thomas Güttler,2,*
Piotr Neumann,1
Achim Dickmanns,1
Dirk Görlich,2,
Ralf Ficner1
CRM1 mediates nuclear export of numerous unrelated cargoes,
which may carry a short leucine-rich nuclear export signal or
export signatures that include folded domains. How CRM1 recognizes
such a variety of cargoes has been unknown up to this point.
Here we present the crystal structure of the SPN1•CRM1•RanGTP
export complex at 2.5 angstrom resolution (where SPN1 is snurportin1
and RanGTP is guanosine 5' triphosphate–bound Ran). SPN1
is a nuclear import adapter for cytoplasmically assembled, m
3G-capped
spliceosomal U snRNPs (small nuclear ribonucleoproteins). The
structure shows how CRM1 can specifically return the cargo-free
form of SPN1 to the cytoplasm. The extensive contact area includes
five hydrophobic residues at the SPN1 amino terminus that dock
into a hydrophobic cleft of CRM1, as well as numerous hydrophilic
contacts of CRM1 to m
3G cap-binding domain and carboxyl-terminal
residues of SPN1. The structure suggests that RanGTP promotes
cargo-binding to CRM1 solely through long-range conformational
changes in the exportin.
2 Abteilung Zelluläre Logistik, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, 37077 Göttingen, Germany.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: goerlich{at}mpibpc.mpg.de
