CHARACTERIZATION OF THE NUCLEAR PORECOMPLEX OF THE AFRICAN TRYPANOSOME

Rockefeller University, New York NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The nuclear pore complex (NPC) is a massive macromolecular assembly, unique to Eukaryotes, that mediates bidirectional exchange of material between the nucleus and cytoplasm. Until recently, the evolutionary origin of the NPC was unknown, leaving a major gap in our understanding of the origin of the Eukaryota. Prior bioinformatic studies led to the conclusion that the Last Common Eukaryotic Ancestor (LCEA) possessed a rather primitive ancestral NPC, passing few components to its highly divergent modern descendants. Using a proteomic/genomic approach, we show that the LCEA actually possessed an NPC with a surprisingly modern architecture. Moreover, we have established that all NPCs have a fundamentally similar scaffold architecture that resembles the architecture of coated vesicles. Our findings strongly support the hypothesis that NPCs share a common ancestry with vesicle coating complexes, and that both were established very early in eukaryotic evolution. A manuscript describing this work has been published (23. J.A. DeGrasse, K.N. DuBois, D. Devos, T.N. Siegel, A. Sali, M.C. Field, M.P. Rout, B.T. Chait "Evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor" Molecular &Cellular Proteomics, 8 (2009) 2119-30).