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The molecular architecture of the nuclear pore complex

Naturevolume 450, pages695–701 (2007)Cite this article

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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Author notes

  1. Svetlana Dokudovskaya, Liesbeth M. Veenhoff, Julia Kipper, Damien Devos, Adisetyantari Suprapto & Orit Karni-Schmidt

    Present address: Present addresses: Laboratory of Nucleocytoplasmic Transport, Institut Jacques Monod, 2 place Jussieu, Tour 43, Paris 75251, France (S.D.); Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands (L.M.V.); German Aerospace Center (PT-DLR), Heinrich-Konen-Strasse 1, D-53227 Bonn, Germany (J.K.); Structural Bioinformatics, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany (D.D.); Office of Technology Transfer, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA (A.S.); Herbert Irving Comprehensive Cancer Centre, Columbia University, 1130 St Nicholas Avenue, New York, New York 10032, USA (O.K.-S.)., New York

  2. Frank Alber, Svetlana Dokudovskaya and Liesbeth M. Veenhoff: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, Mission Bay QB3, 1700 4th Street, Suite 503B, University of California at San Francisco, San Francisco, California 94158-2330, USA, California

    Frank Alber, Damien Devos & Andrej Sali

  2. Laboratory of Cellular and Structural Biology, and,, California

    Svetlana Dokudovskaya, Liesbeth M. Veenhoff, Julia Kipper, Adisetyantari Suprapto, Orit Karni-Schmidt, Rosemary Williams & Michael P. Rout

  3. Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA , New York

    Wenzhu Zhang & Brian T. Chait

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  1. Frank Alber

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  2. Svetlana Dokudovskaya

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  3. Liesbeth M. Veenhoff

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  6. Damien Devos

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  7. Adisetyantari Suprapto

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  8. Orit Karni-Schmidt

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  10. Brian T. Chait

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  11. Andrej Sali

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  12. Michael P. Rout

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Corresponding authors

Correspondence toBrian T. Chait,Andrej Sali orMichael P. Rout.

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Alber, F., Dokudovskaya, S., Veenhoff, L.et al. The molecular architecture of the nuclear pore complex.Nature450, 695–701 (2007). https://doi.org/10.1038/nature06405

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Editorial Summary

Gatekeeper for the Nucleus

The nuclear pore complex plays a crucial role in the cell, as gatekeeper for traffic between the cytoplasm and the interior of the nucleus. It is a large supramolecular complex made up of multiple copies of about 30 different proteins — 456 protein molecules in all. Cell biologists would love to know how each of the pore molecules are placed, but so far this has eluded conventional structural studies. Now, a new proteomics-based technique has provided a detailed view of the architecture of the yeast nuclear pore complex. Half of the complex is made of a core scaffold forming a network coating the surface of the nuclear envelope membrane within which the complex is embedded. The selective transport barrier is formed by the many proteins lining the inner face of the scaffold. Despite its size, there are only a few structural modules in the complex; this underlying simplicity provides possible pointers to an evolutionary origin from a 'primordial' nuclear pore complex. In the cover graphic, the 100-nm diameter pores are shown in the silver-grey nuclear envelope.

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