*********************************
There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
*********************************
School of Physics Soft Condensed Matter & Biophysics Series: Dr. Ajay Gopinathan, University of California, Merced
Intrinsically disordered proteins (IDPs), which form over a third of human proteins, challenge the structure-function paradigm because they function without ever folding into a unique three-dimensional structure. A particularly fascinating example of IDP function is the gating mechanism of the nuclear pore complex (NPC). The NPC is a large macromolecular structure that gates nanoscale pores in the nuclear envelope and controls all nucleo-cytoplasmic traffic such as the import of proteins from the cytoplasm and the export of RNA from the nucleus. The NPC forms a highly selective barrier composed of a large number of IDPs that fill the pore and potentially interact with each other and the cargo.
However, despite numerous studies, the actual structure of the complex within the nuclear pore and its mechanism of operation are poorly understood primarily because of the disordered nature of these proteins. I will present our “bottom-up” approach to understanding the higher-order architecture formed by these proteins using coarse-grained simulations and polymer brush theory. Our results indicate that different regions or “blocks” of an individual NPC protein can have distinctly different forms of disorder and properties and our bioinformatic analysis indicates that this appears to be a conserved feature across all of eukarya. Furthermore, this block structure at the individual protein level is critical to the formation of a unique higher-order polymer brush architecture. Our results indicate that there exist transitions between distinct brush morphologies, which can be triggered by the presence of cargo with specific surface properties which points to a novel form of gated transport in operation within the nuclear pore complex. Insights into this system can potentially be applied to the design of bio-mimetic filters that can achieve highly regulated transport across biological or in vitro membranes.
