A lattice model of the nuclear pore complex

Abstract

The nuclear pore complex (NPC) is one of the largest protein machines in the cell and forms the sole conduit for nucleocytoplasmic transport in eukaryotes. The NPC is composed of an eightfold radially symmetric scaffold of architectural proteins that anchor a set of phenylalanine-glycine (FG) repeat proteins that form the transport barrier. As a step toward elucidating the molecular architecture of the NPC, we solved the structure of nucleoporin 85 (Nup85) in complex with Seh1, a module in the heptameric Nup84 subcomplex. We define a new tripartite protein element, the ancestral coatomer element ACE1, which Nup85 specifically shares with several other nucleoporins and vesicle coat proteins. We predicted and verified functional sites on nucleoporin ACE1 members based on analogy to ACE1 interactions that propagate the COPII vesicle coat. Thus, we provide the first experimental evidence for evolution of the NPC and vesicle coats from a common ancestor. We propose that the NPC structural scaffold, like vesicle coats, is a polygonal network composed of vertex and edge elements that forms a molecular lattice upon which additional nucleoporins assemble. Here we further discuss our findings and elaborate on our lattice model of the nuclear pore complex.