One Ring to Rule them All? Structural and Functional Diversity in the Nuclear Pore Complex

Abstract

The nuclear pore complex (NPC) is the massive protein assembly that regulates the transport of macromolecules between the nucleus and the cytoplasm. Recent breakthroughs have provided major insights into the structure of the NPC in different eukaryotes, revealing a previously unsuspected diversity of NPC architectures. In parallel, the NPC has been shown to be a key player in regulating essential nuclear processes such as chromatin organization, gene expression, and DNA repair. However, our knowledge of the NPC structure has not been able to address the molecular mechanisms underlying its regulatory roles. We discuss potential explanations, including the coexistence of alternative NPC architectures with specific functional roles.

Keywords: NPC; gene regulation; nuclear pore complex; nuclear transport; nucleoporin; structure.

Figure 1.. Structural diversity of nuclear pore complexes (NPCs) across eukaryotes.

Top row, NPC structures for the indicated organisms solved by integrative methods (left S. cerevisiae PDBDEV_00000010–12 [1]), FIB-cryo-ET (right S. cerevisiae EMD-10198 [31], and C. reinhardtii EMD-4355 [32]), cryo-ET (H. sapiens EMD-3103 [47]), or cryo-ET and single particle analysis (X. laevis, kindly shared by Gaoxingyu Huang and Yigong Xi [57, 80]). Middle row, diagrams reflecting the known composition and arrangement of the different nucleoporins (Nups) and NPC modules in S. cerevisiae (left), C. reindhardtii (middle) and H. sapiens (right). The identity of each Nup is shown to the left in S. cerevisiae or to the right of the H. sapiens diagram. Empty, non-colored shapes indicate a non-identified component. Grey arches: nuclear envelope (NE). Bottom row, NPC diagrams showing the outer ring components in red to highlight their alternative arrangement in the different organisms. Bottom right corner, box depicting the protein folds and domains found in Nups. β / α indicates a β-propeller followed by an α-solenoid.