Strukturelle Analyse des bidirektionalen Transportrezeptors Importin13
Final Report Abstract
In eukaryotic cells DNA and transcription of RNAs are segregated from protein production in the cytoplasm. Nucleus and cytoplasm are only connected via the nuclear pores. Transport between these compartments is aided by dedicated shuttling proteins, the karyopherins. Most karyopherins carry cargo only in one direction, either into (importins) or out of the nucleus (exportins), and then return empty handed. Imp13 is an unusual karyopherin that can both import and export cargo. Our work revealed how Imp13 recognizes its cargoes and functions as a bidirectional transport factor. Our work showed the extreme versatility of Imp13 that can recognize cargoes to be imported with non-overlapping recognition interfaces. Structural data confirmed by biochemical experiments showed that even the same import cargo can be recognized in different modification states. How could nuclear transport receptors function in both directions had been an open question in the nuclear transport field. Surprisingly, the mechanism of bidirectionality unveiled by our studies is so simple that it is conceivable that it could be generally adopted by other karyopherins as well. This suggests that the range of bifunctional receptors might be larger than so far appreciated. Dr. Marlene Grünwald, PhD student funded through this grant was awarded several prizes for this work: 2014 Otto-Hahn medal of the Max Planck Society ; 2012 Talk Prize at the Tübingen International PhD Program (TIPP); 2010 Poster Prize at the Murnau Conference on Structural Biology. 2010 Poster Prize at the Tübingen International PhD Program (TIPP)
Publications
- (2011) Assembly, disassembly and recycling: The dynamics of exon junction complexes. RNA Biol., 8:1-6
Bono F. and Gehring N.
- (2011) Structure of Importin13-Ubc9 complex: nuclear import and release of a key regulator of sumoylation. EMBO J., 30:427-38
Grünwald M. and Bono F.
- (2013) Structural basis for the nuclear export activity of Importin13. EMBO J. 32:899-913
Grünwald M, Lazzaretti D, Bono F.
(See online at https://doi.org/10.1038/emboj.2013.29) - (2014) Importin13 – a round trip through the nuclear pore. MPI Yearbook
Bono F.
