Molecular Architecture of the Nuclear Pore Complex

The genomic DNA of eukaryotic cells is surrounded by a double lipid bilayer, the nuclear envelope, which separates the entire nuclear contents from the cytoplasm. The nuclear pore complex (NPC) is a huge macromolecular protein assembly embedded in the nuclear envelope and is the sole gateway of macromolecular traffic between the nucleus and cytoplasm. Regulating the molecular traffic between the nucleus and cytoplasm is essential for various eukaryote-specific cell functions, including fine gene regulation and signal transduction, and thus the NPC functions as a nuclear gatekeeper. Over the last half century, various electron microscopic studies, including cryo-EM reconstruction and atomic-resolution X-ray crystallography, and a combination of these methods with biochemical analysis have revealed the molecular architecture of the NPC in detail. In addition, the analysis using next-generation sequencing has unveiled mutations in nucleoporin genes in an increasing number of hereditary diseases. This article covers the molecular architecture and functions of the NPC, and nucleoporin-related diseases.