Structural basis for RanGTP independent entry of spliceosomal U snRNPs into the nucleus.
The nuclear import of assembled spliceosomal subunits, the uridine-rich small nuclear ribonucleoprotein particles (U snRNPs), is mediated by a nuclear import receptor adaptor couple of importin beta (Imp beta) and snurportin1 (SPN1). In contrast to any other characterized active nuclear import, the Imp beta/SPN1/U snRNP complex does not require RanGTP for the terminal release from the nuclear basket of the nuclear pore complex (NPC). The crystal structure of Imp beta (127-876) in complex with the Imp beta-binding (IBB) domain of SPN1 (1-65) at 2.8-A resolution reveals that Imp beta adopts an open conformation, which is unique for a functional Imp beta/cargo complex, and rather surprisingly, it resembles the conformation of the Imp beta/RanGTP complex. As binding of RanGTP to Imp beta usually triggers the release of import complexes from the NPC, we propose that by already mimicking a conformation similar to Imp beta/RanGTP the independent dissociation of Imp beta/SPN1 from the nuclear basket is energetically aided.
Wohlwend
Daniel
D
Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik and GZMB, Georg-August-Universität Göttingen, Justus-von-Liebig-Weg 11, D-37077 Göttingen, Germany.
Strasser
Anja
A
Dickmanns
Achim
A
Ficner
Ralf
R
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus; D018360:Crystallography, X-Ray; D006801:Humans; D022022:Nuclear Pore / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000502:physiology; D011485:Protein Binding; D039381:RNA Cap-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000502:physiology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism*; D028961:beta Karyopherins / Q000737:chemistry* / Q000502:physiology; D020931:ran GTP-Binding Protein / Q000737:chemistry
D029543:Nucleocytoplasmic Transport Proteins; D039381:RNA Cap-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D017412:Ribonucleoprotein, U1 Small Nuclear; C114090:SNUPN protein, human; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein