Scaffold nucleoporins Nup188 and Nup192 share structural and functional properties with nuclear transport receptors

The nucleus of a cell is surrounded by a two-layered membrane that controls the flow of molecules from the cytoplasm into the nucleus and vice versa. The molecular traffic between the cytoplasm and nucleus is essentially controlled by nuclear pore complexes—large, multi-protein structures that are embedded in the membrane. Each nuclear pore complex contains about 30 different proteins called nucleoporins or nups, which combine to form a structure with a central pore that allows the molecules to enter and leave the nucleus. The centre of the nuclear pore complex is thought to be filled with protein filaments that contain a large number of so-called FG repeats (where F and G are the amino acids phenylalanine and glycine). Specialized molecules called soluble nuclear transport receptors, which carry various cargoes between the cytoplasm and nucleus, can bind to these FG repeats, and the interaction between the receptors and the FG repeats is crucial for the selective transport of molecules between the cytoplasm and the nucleus. The large size of the nuclear pore complex has hindered efforts to work out its structure, but in recent years researchers have been able to obtain structures for many individual nups and their subcomplexes. Now, Andersen et al. have determined the structure of one of the largest nups, Nup188. This has led to the discovery that it and a related nup, Nup192, share unexpected features with soluble nuclear transport receptors. In general the first step when attempting to determine the structure of a biomolecule is to form a crystal. Since full-length Nup188 did not crystallize, Andersen et al. instead crystallized two large fragments of Nup188, determined the structures of these fragments, and then combined these to produce the likely structure of the full-length protein. They found that Nup188 has a structure that consists of stacked helices and is more flexible than other nups. Moreover, its structure was very similar to those of soluble nuclear transport receptors, and this led Andersen et al. to investigate whether Nup188 also had similar functional features. Surprisingly, they discovered that both Nup188 and Nup192 could bind FG repeats, just like nuclear transport receptors. What is more, this binding allowed both nups to travel through nuclear pore complexes in in vitro transport reactions. These findings have implications for the understanding of the organization and function of FG-repeats and suggest that the stationary elements of the nuclear pore complex and soluble nuclear transport receptors are evolutionarily related.