Structure Determination of the Nuclear Pore Complex with Three-Dimensional Cryo electron Microscopy

Determining the structure of the nuclear pore complex (NPC) imposes an enormous challenge due to its size, intricate composition and membrane-embedded nature. In vertebrates, about 1000 protein building blocks assemble into a 110-MDa complex that fuses the inner and outer membranes of a cell's nucleus. Here, we review the recent progress in understanding the in situ architecture of the NPC with a specific focus on approaches using three-dimensional cryo electron microscopy. We discuss technological benefits and limitations and give an outlook toward obtaining a high-resolution structure of the NPC.