Bidirectional macromolecular traffic between the cytoplasm and the nucleus occurs exclusively through the Nuclear Pore Complex (NPC). In mammalian cells, the NPC has a molecular mass of about 100 million daltons and is located in circular openings (100 nm diameter) of the nuclear envelope. Thirty proteins form a pseudo-symmetric structure with an eight-fold symmetry in a nucleo-cytoplasmic axis and a two-fold symmetry in the plane of the nuclear envelope. Architecturally, the NPC is composed of eight spokes that emanate from a central channel (40 nm diameter) and connect to the pore membrane, the sharp bend connecting the inner and outer nuclear envelope membrane.

Crystallographic analysis has revealed that some proteins that line the central channel of the NPC contain highly conserved amphipathic alpha helices with large hydrophilic residues on one side of the helix. In a tetramer of the nucleoporin Nup58/45, the large hydrophilic residues of two antiparallel helices, each from one monomer, form one surface that interacts with two antiparallel helices, each from one monomer, in the other opposing surface. Distinct laterally displaced conformers in the tetramers were detected in the same crystal, suggesting sliding of helical surfaces along an 11 Angstrom pathway. As eight tetramers are circumferentially arranged around the central transport channel of the NPC, sliding of each tetramer would result in a flexible diameter of the central channel of the NPC.