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Toward the atomic structure of the nuclear pore complex: when top down meets bottom up

Nature Structural & Molecular Biology volume 23, pages 624–630 (2016)Cite this article

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Abstract

Elucidating the structure of the nuclear pore complex (NPC) is a prerequisite for understanding the molecular mechanism of nucleocytoplasmic transport. However, owing to its sheer size and flexibility, the NPC is unapproachable by classical structure determination techniques and requires a joint effort of complementary methods. Whereas bottom-up approaches rely on biochemical interaction studies and crystal-structure determination of NPC components, top-down approaches attempt to determine the structure of the intact NPC in situ. Recently, both approaches have converged, thereby bridging the resolution gap from the higher-order scaffold structure to near-atomic resolution and opening the door for structure-guided experimental interrogations of NPC function.

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Figure 1: General organization principles of nuclear pores and the Y-shaped CNC.
Figure 2: The structural organization of the CNC in situ is consistent with structural analysis in vitro.
Figure 3: Gene silencing of Nup358 causes loss of the outer CNC in the cytoplasmic ring.
Figure 4: Schematic representation of the CNC arrangement in the intact NPC.

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Acknowledgements

We thank A. Patke for critical reading of the manuscript and A. von Appen and J. Kosinski for help with preparing the figures. A.H. was supported as an inaugural Heritage Principal Investigator of the Heritage Research Institute for the Advancement of Medicine and Science at Caltech and was supported by Caltech startup funds, an Albert Wyrick V Scholar Award from the V Foundation for Cancer Research, the 54th Mallinckrodt Scholar Award from the Edward Mallinckrodt Jr. Foundation, a Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research, a Camille-Dreyfus Teacher Scholar Award from The Camille & Henry Dreyfus Foundation, and National Institutes of Health (NIH) grants R01-GM111461 and R01-GM117360. J.S.G. was supported by National Institute on Aging (NIA) grant R21-AG047433. M.B. acknowledges funding from the EMBL and the European Research Council (309271-NPCAtlas).

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Authors and Affiliations

  1. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA

    André Hoelz

  2. Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey, USA

    Joseph S Glavy

  3. European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany

    Martin Beck

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Correspondence to André Hoelz, Joseph S Glavy or Martin Beck.

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Hoelz, A., Glavy, J. & Beck, M. Toward the atomic structure of the nuclear pore complex: when top down meets bottom up. Nat Struct Mol Biol 23, 624–630 (2016). https://doi.org/10.1038/nsmb.3244

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