Dynamic Structures of the Nuclear Pore Complex and Their Roles in Nucleocytoplasmic Transport

Abstract

The structure of the NPC has been studied for over 60 years. Although we are beginning to understand its structural framework, we do not know how the structure acts as a selective gate and how it facilitates transport in either direction. This may be because the very components that directly facilitate gating are varied, dynamic and possibly amorphous. Here, what we know about the structural organisation of the peripheral and dynamic components, such as the cytoplasmic filaments, the NPC basket and the structures within and protruding from the central channel, is reviewed in relation to their roles in nuclear transport. 3.1 Introduction: The NPC Consists of a Rigid Scaffold and Dynamic Peripheral and Central Structures The nuclear pore complex (NPC) is a large complex structure stabilising an annulus created by the fusion of the inner and outer nuclear membranes to form a communication channel between nuclear and cytoplasmic compartments. With a combination of electron microscopy (EM), cryo-electron tomography, interaction studies and structural analysis, we are approaching an atomic model of the NPC scaffold (Beck and Hurt 2017). Conversely, peripheral components of the NPC, such as cytoplas-mic filaments and nucleoplasmic basket/fishtrap, are dynamic, variable and not amenable to high-resolution structural analysis. Such components were instead discovered and studied with "molecular resolution" methods such as scanning electron microscopy (SEM) (Ris 1989; Goldberg and Allen 1992; Fig. 3.1), metal shadow transmission EM (TEM) and atomic force microscopy (AFM). Likewise the structural organisation of the selective barrier, located within, and possibly around, the central channel, is uncertain, despite intense study, analysis and discussion. The selective barrier is thought to consist of intrinsically disordered domains (IDDs) of so-called FG-nucleoporins (Radu et al. 1995), which are presumed to have highly