Nuclear transport at full amino-acid resolution

Abstract

AbstractRecent studies of nuclear pore complexes (NPCs) have provided detailed descriptions of the core scaffold structures, yet fall short in resolving the dynamic FG-meshwork with similar pre-cision. Here, we present a novel modeling framework that enables the simulation of nuclear transport at full amino-acid resolution. We describe the distributions of the different FG-Nups in the central transporter and highlight the dynamic nature of the FG-meshwork, with FG–FG interaction lifetimes on the order of nanoseconds. Our findings reveal that Nsp1, the most abundant FG-Nup in the NPC, creates a central meshwork due to its unique bimodal structure, that is essential for controlling both passive and active transport. By introducing nuclear transport receptors (NTRs)—in the form of Kap95—to the pore, we demonstrate that NTRs play a key role in increasing the energy barrier for translocation of inert particles. We observe a dynamic interplay between high affinity binding to FG-motifs and the temporal fluctuations of the FG-meshwork, leading to local low-density pockets, so-called voids, through which Kaps move. Furthermore, we show that the introduction of Kaps to the FG-meshwork results in a clear “dirty velcro” mechanism with slower Kaps decorating the sticky surface of the high-density GLFG-assembly, thus enabling fast translocation of Kaps through the center of the pore.