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NPCATLAS Report Summary

Project ID: 309271
Funded under: FP7-IDEAS-ERC
Country: Germany

Final Report Summary - NPCATLAS (Atlas of Cell-Type Specific Nuclear Pore Complex Structures)

Nuclear Pore Complexes (NPCs) are very large macromolecular assemblies that facilitate the exchange of macromolecules between the cytoplasm and nucleus of all eukaryotic cells. NPCAtlas aims to elucidate how the structure of the human nuclear pore complex (NPC) is altered across different biological states, such as e.g. different cell-types. Structure determination of huge macromolecular assemblies such as the NPCs requires the integration of various types of experimental data. NPCAtlas aimed to facilitate data integration efforts as a joint effort of the scientific field.
We have found that ~1000 protein building blocks are required to assemble a single human nuclear pore complex. However, we also found in line with research conducted by other groups, that the composition of the nuclear pore is variable in healthy and diseased cell types. Most but not all of its components are ubiquitously present – likely to adapt the transport capacity to context specific needs. To elucidate the architectural organization of the components of the nuclear pore we have used mass spectrometric and cryo electron microscopic approaches. Using these technologies we have recently determined the architectural arrangement of more than 600 protein building blocks within the outer and inner rings of the nuclear pore, which comprises a considerable part of its structure. We found that Nup358, which varies in its expression levels across healthy and diseased cell-types, has a critical contribution to the architectural arrangement and causes structural alterations when removed by gene silencing. These data provide a first glimpse onto its possible structural rearrangements of the NPC.

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