Architecture of the nuclear pore inner ring complex

The nuclear pore complex (NPC) constitutes the sole gateway for bidirectional nucleocytoplasmic transport. We present the reconstitution and interdisciplinary analyses of the ~425-kDa inner ring complex (IRC), which forms the central transport channel and diffusion barrier of the NPC, revealing its interaction network and equimolar stoichiometry. The Nsp1•Nup49•Nup57 channel nucleoporin hetero-trimer (CNT) attaches to the IRC solely through the adaptor nucleoporin Nic96. The CNT•Nic96 structure reveals that Nic96 functions as an assembly sensor that recognizes the three dimensional architecture of the CNT, thereby mediating the incorporation of a defined CNT state into the NPC. We propose that the IRC adopts a relatively rigid scaffold that recruits the CNT to primarily form the diffusion barrier of the NPC, rather than enabling channel dilation. One of the great hallmarks of eukaryotic evolution is the enclosure of genetic information in the nucleus. The spatial segregation of replication and transcription in the nucleus from translation in the cytoplasm imposes the requirement of transporting thousands of macromolecules between these two compartments. Nuclear pore complexes (NPCs) are massive transport channels that allow bidirectional macromolecular exchange across the nuclear envelope (NE) and thus function as key regulators of the flow of genetic information from DNA to RNA to protein (1). Correspondence: hoelz@caltech.edu (A.H.). 4these authors contributed equally to this work †present address: Max-Planck-Institute of Biophysical Chemistry, Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany The authors declare no financial conflicts of interest. Supplementary Materials: Materials and Methods Figures S1–S38 Tables S1–S9 Movies S1–S4 References (42–77) HHS Public Access Author manuscript Science. Author manuscript; available in PMC 2016 April 11. Published in final edited form as: Science. 2015 October 2; 350(6256): 56–64. doi:10.1126/science.aac9176. A uhor M anscript