Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex

The Nuclear Pore Complex (NPC) mediates nucleocytoplasmic transport in all eukaryotes and is among the largest cellular assemblies of proteins, collectively referred to as nucleoporins (nups). Nups are organized into distinct subcomplexes. We optimized the isolation of a putative membrane-coating subcomplex of the NPC, the heptameric Nup84 complex, and analyzed its structure by electron microscopy (EM). Our data confirm the previously reported Y-shape. We discerned additional structural details, including specific hinge regions at which the particle shows great flexibility. We determined the three-dimensional structures of two conformers, mapped the localization of two nups within the subcomplex and docked known crystal structures into the EM maps. The free ends of the Y-shaped particle are formed by beta-propellers; the connecting segments consist of alpha-solenoids. Strikingly, the same organizational principle is found in the clathrin triskelion, which was proposed to share a common evolutionary origin with the heptameric complex.