Bayliss, R., Littlewood, T. & Stewart, M. (2000)
Structural basis for the interaction between importin-beta and nucleoporin FxFG repeats in nuclear trafficking.
Cell, 102, 99-108.
Matsuura, Y. & Stewart, M. (2004)
Structural basis for the assembly of a nuclear export complex.
Nature, 432, 872-877.
Lee, S.J., Matsuura, Y., Liu, S.M. & Stewart, M. (2005)
Structural basis for nuclear import complex disassembly by RanGTP.
Nature, 435, 693-696.
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Group Members
- Neil Marshall
- Divyang Jani
- Jack Dean
- Sonja Kuhlmann
- Rhian Holvey
- Eugene Valkov
- Shintaro Aibara
- Birthe Meineke
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| Proteins and nucleic acids are transported between the cytoplasm and nucleus through nuclear pores, huge disc-shaped macromolecular assemblies about 125nm in diameter that perforate the nuclear envelope. Cargo macromolecules are transported through the pores by specific carrier molecules and this process is often orchestrated by the Ran GTPase. Our longterm goal is to understand the nuclear transport machinery at the molecular level. To do this, a combination of structural, molecular and cellular methods is being used to establish the structure of the proteins involved and how they interact with one another to generate transport. |
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Thus, the structures of a range of transport factors together with their complexes with nuclear pore proteins (nucleoporins), cargoes and Ran have been established by crystallography or NMR. This structural information has then been used to engineer specific mutants that have been used to define the role of each interaction in the overall process.
| Future work will concentrate on three main areas. The first is to address the role of nucleoporins containing distinctive FG sequence repeats in the assembly and disassembly of transport complexes and also in preventing inappropriate transport through nuclear pores.
Second, we will explore the role of nuclear trafficking in signalling, especially in the context of b-catenin and the Wnt pathway. Third, we will investigate the role of nuclear trafficking components and small proteins such as Sus1p and Nab2p in orchestrating the gene expression machinery, especially in the context of their acting as scaffolds for the formation of the large macromolecular complexes involved in transcription, splicing, mRNA processing and nuclear export. In each case, we will aim to use X-ray crystallography, NMR and EM to obtain the structure of the components and their interaction interfaces, and then use this information to generate mutants that can address the functional importance of these interactions.
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Group Leaders 
