Overview
Research in our lab aims at understanding protein function on the basis of atomic structure determination using X-ray crystallography as the main tool. Our focal point is the elucidation of the structure of the Nuclear Pore Complex (NPC), the only gateway into and out of the cell nucleus and thus of central importance for eukaryotic cell survival. We employ an integrative approach to this research area combining structure determination with biochemical, biophysical, cell biological and genetic methods.

Research Summary
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 are trying to understand the workings of this nanomachine. To do so, we first attempt to solve the structure of the NPC. 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. Despite this progress, much work needs to be done to fully understand the NPC assembly. Yet, we can now already use the gained structural information to engineer probes that allow for dissecting NPC function in unprecedented precision. 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 in the future.

Selected Publications
Boehmer, T., Jeudy, S., Berke, I.C. & Schwartz, T.U. (2008) Structural and Functional Studies of Nup107/Nup133 Interaction and Its Implications for the Architecture of the Nuclear Pore Complex. Mol. Cell, 30, 721-731.

Jeudy, S. & Schwartz, T.U. (2007) Crystal structure of nucleoporin Nic96 reveals a specifically conserved, intricate helical domain architecture. J. Biol. Chem., 282, 34904-34912.

Schwartz, T.U. (2005). Modularity within the Architecture of the Nuclear Pore Complex. Curr. Op. Struct. Biol., 15, 221-226.

Berke, I.C., Boehmer, T., Blobel, G. & Schwartz, T.U. (2004). Structural and Functional Analysis of Nup133 Domains Reveals Modular Building Blocks of the Nuclear Pore Complex. J. Cell Biol., 167, 591-597.

Schwartz, T. & Blobel, G. (2003). Structural Basis for the Function of the b Subunit of the Eukaryotic Signal Recognition Particle Receptor. Cell, 112, 793-803.

Schwartz, T., Rould, M.A., Lowenhaupt, K., Herbert, A. & Rich, A. (1999). Crystal Structure of the Za Domain of the Human Editing Enzyme ADAR1 Bound to Left-Handed Z-DNA. Science 284, 1841-1845.

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