Global Motions of the Nuclear Pore Complex: Insights from Elastic Network Models

The nuclear pore complex (NPC) is the gate to the nucleus. Recent determination of the configuration of proteins in the yeast NPC at ∼5 nm resolution permits us to study the NPC global dynamics using coarse-grained structural models. We investigate these large-scale motions by using an extended elastic network model (ENM) formalism applied to several coarse-grained representations of the NPC. Two types of collective motions (global modes) are predicted by the ENMs to be intrinsically favored by the NPC architecture: global bending and extension/contraction from circular to elliptical shapes. These motions are shown to be robust against tested variations in the representation of the NPC, and are largely captured by a simple model of a toroid with axially varying mass density. We demonstrate that spoke multiplicity significantly affects the accessible number of symmetric low-energy modes of motion; the NPC-like toroidal structures composed of 8 spokes have access to highly cooperative symmetric motions that are inaccessible to toroids composed of 7 or 9 spokes. The analysis reveals modes of motion that may facilitate macromolecular transport through the NPC, consistent with previous experimental observations.Author Summary: The nuclear pore complex (NPC) serves as the sole gateway to the cell nucleus, and its proper functioning is therefore crucial for gene expression and many vital signaling pathways. Although it is typically circular, the overall structure of the NPC has been observed to change in response to the presence of cargo. Recently, the molecular architecture of the yeast NPC, including the shapes and relative positions of its constituent proteins, has been resolved. These new structural data provide us with a first opportunity to construct an accurate dynamical model of a macromolecular machine containing hundreds of proteins. By modeling the NPC as a network of masses connected by springs, we investigate its probable large-scale dynamics. We start from a very coarse model and gradually refine it, observing how the structural details influence the calculated dynamics. We find that the NPC dynamics are quite similar to those of a flexible toroid with an uneven mass distribution, and that the 8-fold symmetry that is universally observed in NPCs enables them to undergo certain collective motions that are inaccessible to structures of other symmetries.