Daniel Lin, Tobias Stuwe, Ana R. Correia, Marcin Paduch, Vincent T. Lu, Anthony A. Kossiakoff, and André Hoelz

California Institute of Technology

The nuclear pore complex (NPC) constitutes the sole gateway for bidriectional nucleocytoplasmic transport. Despite half a century of structural characterization, the architecture of the NPC remains unknown. Here, we present the crystal structure of a reconstituted ~400 kDa coat nucleoporin complex (CNC) from S. cerevisiae at 7.4-Å resolution. The crystal structure revealed a curved Y-shaped architecture and the molecular details of the coat nucleoporin interactions forming the central "triskelion" of the Y. A structural comparison of the yeast CNC with an electron microscopy reconstruction of its human counterpart suggested the evolutionary conservation of the elucidated architecture. Moreover, thirty-two copies of the CNC crystal structure docked readily into a cryoelectron tomographic reconstruction of the full-assembled human NPC, thereby accounting for ~16 MDa of its mass.