Schedule May 27, 2011
Intrinsically Disordered Polymer Brushes and the Nuclear Pore Complex: Implications for a Novel Form of Gated Transport
Ajay Gopinathan (UC Merced)

Ajay Gopinathan, School of Natural Sciences,
University of California, Merced

A particular membrane that sees a lot of cross-membrane traffic is the nuclear envelope in eukaryotes. The nuclear pore complex (NPC) is an important macromolecular structure that gates the aqueous pores between the cytoplasm and nucleoplasm of cells and controls all nucleo-cytoplasmic transport and communication such as the import of proteins from the cytoplasm and the export of RNA from the nucleus. The NPC forms a barrier that maintains a tight seal against cytoplasmic particles larger than 4 nm while simultaneously allowing the facilitated transport of specially “tagged” particles up to 40 nm in diameter, at speeds comparable to free diffusion! The key to the selectivity is hypothesized to be due to a large number of NPC proteins that fill the pore and potentially interact with each other and the cargo. However, despite numerous studies on the structure and properties of individual NPC proteins, the actual structure of the complex within the nuclear pore and its mechanism of operation are virtually unknown with leading models of nuclear pore transport assuming vastly different morphologies for the NPC protein complex filling the nuclear pore. Here, we use a bottom-up approach, applying the physics of polymer brushes to understand the three dimensional architecture of the complex based on our recent experimental understanding of the properties of individual NPC proteins. Our results indicate that there exist transitions between distinct brush morphologies (open and closed states of the gate), which can be triggered by the presence of cargo with specific surface properties. This has led to development of the Discrete Gate Model - an experimental data driven theoretical model. The resulting transport mechanism, that we propose, is fundamentally different from existing models and points to a novel form of gated transport in operation within the nuclear pore complex. Our results can also be extended to designing and optimizing novel forms of biomimetic transport based on this mechanism.

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