From the trap to the basket: getting to the bottom of the nuclear pore complex |
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Authors: | Roderick Y H Lim Ueli Aebi Daniel Stoffler |
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Institution: | (1) M.E. Müller Institute for Structural Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland |
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Abstract: | Nuclear pore complexes (NPCs) are large supramolecular assemblies that perforate the double-membraned nuclear envelope and
serve as the sole gateways of molecular exchange between the cytoplasm and the nucleus in interphase cells. Combining novel
specimen preparation regimes with innovative use of high-resolution scanning electron microscopy, Hans Ris produced in the
late eighties stereo images of the NPC with unparalleled clarity and structural detail, thereby setting new standards in the
field. Since that time, efforts undertaken to resolve the molecular structure and architecture, and the numerous interactions
that occur between NPC proteins (nucleoporins), soluble transport receptors, and the small GTPase Ran, have led to a deeper
understanding of the functional role of NPCs in nucleocytoplasmic transport. In spite of these breakthroughs, getting to the
bottom of the actual cargo translocation mechanism through the NPC remains elusive and controversial. Here, we review recent
insights into NPC function by correlating structural findings with biochemical data. By introducing new experimental and computational
results, we reexamine how NPCs can discriminate between receptor-mediated and passive cargo to promote vectorial translocation
in a highly regulated manner. Moreover, we comment on the importance and potential benefits of identifying and experimenting
with individual key components implicated in the translocation mechanism. We conclude by dwelling on questions that we feel
are pertinent to a more rational understanding of the physical aspects governing NPC mechanics. Last but not least, we substantiate
these uncertainties by boldly suggesting a new direction in NPC research as a means to verify such novel concepts, for example,
a de novo designed ‘minimalist’ NPC.
This article is dedicated to the memory of Hans Ris. |
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