Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP.
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(3)G-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(3)G 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.
Monecke
Thomas
T
Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik, GZMB, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
Güttler
Thomas
T
Neumann
Piotr
P
Dickmanns
Achim
A
Görlich
Dirk
D
Ficner
Ralf
R
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D028884:Karyopherins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D039381:RNA Cap-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000737:chemistry* / Q000378:metabolism; D000097606:Exportin 1 Protein
D006160:Guanosine Triphosphate; D028884:Karyopherins; D039381:RNA Cap-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C120587:RAN protein, human; C114090:SNUPN protein, human