Structure and nucleic acid binding activity of the nucleoporin Nup157

Abstract

At the center of the nuclear pore complex (NPC) is a uniquely versatile central transport channel. Structural analyses of distinct segments (“protomers”) of the three “channel” nucleoporins yielded a model for how this channel is constructed. Its principal feature is a midplane ring that can undergo regulated diameter changes of as much as an estimated 30 nm. To better understand how a family of “adaptor” nucleoporins—concentrically surrounding this channel—might cushion these huge structural changes, we determined the crystal structure of one adaptor nucleoporin, Nup157. Here, we show that a recombinant Saccharomyces cerevisiae Nup157 protomer, representing two-thirds of Nup157 (residues 70–893), folds into a seven-bladed β-propeller followed by an α-helical domain, which together form a C-shaped architecture. Notably, the structure contains a large patch of positively charged residues, most of which are evolutionarily conserved. Consistent with this surface feature, we found that Nup157_70–893 binds to nucleic acids, although in a sequence-independent manner. Nevertheless, this interaction supports a previously reported role of Nup157, and its paralogue Nup170, in chromatin organization. Based on its nucleic acid binding capacity, we propose a dual location and function of Nup157. Finally, modeling the remaining C-terminal portion of Nup157 shows that it projects as a superhelical stack from the compact C-shaped portion of the molecule. The predicted four hinge regions indicate an intrinsic flexibility of Nup157, which could contribute to structural plasticity within the NPC. Significance The nuclear pore complex (NPC) is a multiprotein gating complex that allows for bidirectional transport across the nuclear membrane. A key feature of the NPC is a central transport channel that can undergo regulated diameter changes, thus enabling the trafficking of cargo of various sizes. Surrounding this channel is a group of proteins, named “adaptor” nucleoporins, which are envisioned to accommodate and orchestrate these structural changes. Here we show the crystal structure of a fragment of an adaptor nucleoporin, Nup157, which forms a compact C-shaped architecture. Notably, Nup157 contains a positively charged surface consistent with its nucleic acid binding capacity. Furthermore, the predicted hinge regions in Nup157 suggest its flexibility in agreement with the plastic nature of the NPC.