The Nuclear Pore Complex

In eukaryotes, genes are transcribed from DNA into RNA in the nucleus, whereas proteins are synthesized in the cytoplasm. For mRNA transcripts to exit the nucleus and protein molecules to enter back in they need to traverse the double-layered nuclear envelope membrane. This highly controlled process is exclusively facilitated by the Nuclear Pore Complex (NPC), a vast protein assembly residing in circular openings in the nuclear envelope. We aim to understand this nanomachine in molecular detail. Multiple copies of roughly 30 different proteins (nucleoporins or nups), in total ~500 individual molecules or 40-60MDa in mass, make up an NPC. Nups are organized into distinct subcomplexes that assemble to form the entire structure. In combining X-ray crystallographic techniques, amenable to the study of these subcomplexes, with electron-microscopic methods applied to larger assemblies, we are visualizing the NPC. So far our results have led to a detailed picture of the modular nature of the NPC and we have elucidated important design principles, all based on experimental evidence. We have elucidated a surprisingly close structural relationship between the NPC and specific vesicular coat proteins pointing to common evolutionary ancestry. Step by step these results allow us to dissect and assign the functions of the NPC. We are now interested in the interplay between various transport systems in the cell for which evidence is mounting. A myriad of functions besides its role in transport, for example in nuclear organization and gene regulation, place the NPC in the center of cell biology, yet are so far only vaguely understood. These topics represent major directions we are interested in exploring.