Integrated structural analysis of the human nuclear pore complex scaffold

Bui, Khanh Huy; von Appen, Alexander; DiGuilio, Amanda L.; Ori, Alessandro; Sparks, Lenore; Mackmull, Marie-Therese; Bock, Thomas; Hagen, Wim; Andrés-Pons, Amparo; Glavy, Joseph S.; Beck, Martin

doi:10.1016/j.cell.2013.10.055

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Integrated structural analysis of the human nuclear pore complex scaffold

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Bui, K. H., von Appen, A., DiGuilio, A. L., Ori, A., Sparks, L., Mackmull, M.-T., et al. (2013). Integrated structural analysis of the human nuclear pore complex scaffold. Cell, 155(6), 1233-1243. doi:10.1016/j.cell.2013.10.055.

Cite as: https://hdl.handle.net/21.11116/0000-0006-D519-E

Abstract

The nuclear pore complex (NPC) is a fundamental component of all eukaryotic cells that facilitates nucleocytoplasmic exchange of macromolecules. It is assembled from multiple copies of about 30 nucleoporins. Due to its size and complex composition, determining the structure of the NPC is an enormous challenge, and the overall architecture of the NPC scaffold remains elusive. In this study, we have used an integrated approach based on electron tomography, single-particle electron microscopy, and crosslinking mass spectrometry to determine the structure of a major scaffold motif of the human NPC, the Nup107 subcomplex, in both isolation and integrated into the NPC. We show that 32 copies of the Nup107 subcomplex assemble into two reticulated rings, one each at the cytoplasmic and nuclear face of the NPC. This arrangement may explain how changes of the diameter are realized that would accommodate transport of huge cargoes.