Implications of a multiscale structure of the yeast nuclear pore complex

Christopher W Akey; Ignacia Echeverria; Christna Ouch; Ilona Nudelman; Yi Shi; Junjie Wang; Brian T Chait; Andrej Sali; Javier Fernandez-Martinez; Michael P Rout

doi:10.1016/j.molcel.2023.08.025

Implications of a multiscale structure of the yeast nuclear pore complex

Mol Cell. 2023 Sep 21;83(18):3283-3302.e5. doi: 10.1016/j.molcel.2023.08.025.

Authors

Affiliations

¹ Department of Pharmacology, Physiology and Biophysics, Boston University, Chobanian and Avedisian School of Medicine, 700 Albany Street, Boston, MA 02118, USA. Electronic address: cakey@bu.edu.
² Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
³ Department of Pharmacology, Physiology and Biophysics, Boston University, Chobanian and Avedisian School of Medicine, 700 Albany Street, Boston, MA 02118, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 01605, USA.
⁴ Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
⁵ Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, USA.
⁶ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
⁷ Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA; Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, 48940 Leioa, Spain.
⁸ Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: rout@rockefeller.edu.

Abstract

Nuclear pore complexes (NPCs) direct the nucleocytoplasmic transport of macromolecules. Here, we provide a composite multiscale structure of the yeast NPC, based on improved 3D density maps from cryogenic electron microscopy and AlphaFold2 models. Key features of the inner and outer rings were integrated into a comprehensive model. We resolved flexible connectors that tie together the core scaffold, along with equatorial transmembrane complexes and a lumenal ring that anchor this channel within the pore membrane. The organization of the nuclear double outer ring reveals an architecture that may be shared with ancestral NPCs. Additional connections between the core scaffold and the central transporter suggest that under certain conditions, a degree of local organization is present at the periphery of the transport machinery. These connectors may couple conformational changes in the scaffold to the central transporter to modulate transport. Collectively, this analysis provides insights into assembly, transport, and NPC evolution.

Keywords: AlphaFold2 modeling; FG repeats; computed structure models; cryo-EM; cryogenic electron microscopy; nuclear pore complex; nucleocytoplasmic transport; single-particle analysis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Membrane Transport Proteins
Nuclear Pore*
Saccharomyces cerevisiae* / genetics

Substances

Membrane Transport Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding