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The molecular architecture of the nuclear pore complex

Abstract

Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50 MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the NPC’s 456 constituent proteins (see the accompanying paper). Our structure reveals that half of the NPC is made up of a core scaffold, which is structurally analogous to vesicle-coating complexes. This scaffold forms an interlaced network that coats the entire curved surface of the nuclear envelope membrane within which the NPC is embedded. The selective barrier for transport is formed by large numbers of proteins with disordered regions that line the inner face of the scaffold. The NPC consists of only a few structural modules that resemble each other in terms of the configuration of their homologous constituents, the most striking of these being a 16-fold repetition of ‘columns’. These findings provide clues to the evolutionary origins of the NPC.

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Figure 1: Architectural overview of the NPC.
Figure 2: Localization of major substructures and their component nucleoporins in the NPC.
Figure 3: The core scaffold as a membrane-coating complex.
Figure 4: Distribution of the disordered FG-repeat regions in the NPC.
Figure 5: Modular duplication in the NPC.

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Acknowledgements

We thank H. Shio for performing the electron microscopic studies; J. Fanghänel, M. Niepel and C. Strambio-de-Castillia for help in developing the affinity purification techniques; M. Magnasco for discussions and advice; A. Kruchinsky for assistance with mass spectrometry; M. Topf, D. Korkin, F. Davis, M. S. Madhusudan, M.-Y. Shen, F. Foerster, N. Eswar, M. Kim, D. Russell, B. Peterson and B. Webb for many discussions about structure characterization by satisfaction of spatial restraints; C. Johnson, S. G. Parker, and C. Silva, T. Ferrin and T. Goddard for preparation of some figures; and S. Pulapura and X. J. Zhou for their help with the design of the conditional diameter restraint. We are grateful to J. Aitchison for discussion and suggestions. We also thank all other members of the Chait, Rout and Sali laboratories for their assistance. We acknowledge support from an Irma T. Hirschl Career Scientist Award (M.P.R.), a Sinsheimer Scholar Award (M.P.R.), a grant from the Rita Allen Foundation (M.P.R.), a grant from the American Cancer Society (M.P.R.), the Sandler Family Supporting Foundation (A.S.), the Human Frontier Science Program (A.S., L.M.V.), NSF (A.S.), and grants from the National Institutes of Health (B.T.C., M.P.R., A.S.), as well as computer hardware gifts from R. Conway, M. Homer, Intel, Hewlett-Packard, IBM and Netapp (A.S.).

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Alber, F., Dokudovskaya, S., Veenhoff, L. et al. The molecular architecture of the nuclear pore complex. Nature 450, 695–701 (2007). https://doi.org/10.1038/nature06405

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