Cited by 180Nuclear Structure and FunctionProtein Structure and DynamicsMicrotubule and mitosis dynamics

Comprehensive structure and functional adaptations of the yeast nuclear pore complex

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Akey, Christopher W., Singh, Digvijay, Ouch, Christna, Echeverria, Ignacia, Nudelman, Ilona, Varberg, Joseph M., Yu, Zulin, Fang, Fei +15 more·2022·Cell

Published version of a preprint

Abstract

Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the isolated yeast NPC in which the inner ring is resolved by cryo-EM at sub-nanometer resolution to show how flexible connectors tie together different structural and functional layers. These connectors may be targets for phosphorylation and regulated disassembly in cells with an open mitosis. Moreover, some nucleoporin pairs and transport factors have similar interaction motifs, which suggests an evolutionary and mechanistic link between assembly and transport. We provide evidence for three major NPC variants that may foreshadow functional specializations at the nuclear periphery. Cryo-electron tomography extended these studies, providing a model of the in situ NPC with a radially expanded inner ring. Our comprehensive model reveals features of the nuclear basket and central transporter, suggests a role for the lumenal Pom152 ring in restricting dilation, and highlights structural plasticity that may be required for transport.

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Authors
Akey, C. W., Singh, D., Ouch, C., Echeverria, I., Nudelman, I., Varberg, J. M., Yu, Z., Fang, F., Shi, Y., Wang, J., Salzberg, D., Song, K., Xu, C., Gumbart, J. C., Suslov, S., Unruh, J., Jaspersen, S. L., Chait, B. T., Sali, A., Fernandez-Martinez, J., Ludtke, S. J., Villa, E., & Rout, M. P.
Affiliations
  • Boston University (US)
  • University of California San Diego (US)
  • University of California, San Francisco (US)
  • Rockefeller University (US)
  • Stowers Institute for Medical Research (US)
  • University of Pittsburgh (US)
  • University of Massachusetts Chan Medical School (US)
  • Georgia Institute of Technology (US)
  • Baylor College of Medicine (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Akey, Christopher W.
  • Ludtke, Steven J.
  • Villa, Elizabeth
  • Rout, Michael P.
Venue
Cell
Publisher
Elsevier BV
Published
2022-01
Volume
185
Issue
2
Pages
361-378.e25
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4220942300
Cited by
180
References
1
Citations by year
2026: 18 · 2025: 33 · 2024: 41 · 2023: 48 · 2022: 39 · 2021: 1
FWCI
13.14
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
  • Howard Hughes Medical Institute
  • PEW Charitable Trusts
  • Damon Runyon Cancer Research Foundation
  • NSF
  • Israel National Road Safety Authority
  • National Institutes of Health (DP2 GM123494, F32 GM133096, NSF-1818129, P01 GM121203, P41 GM109824, R01 GM112108, R01 GM117212, R01 GM121443, R01 GM45377)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
nuclear pore complex, nuclear transport, yeast, nucleoporins, nuclear basket, open mitosis, phosphorylation, cryo-electron tomography, structural plasticity
MeSH terms
Protein Domains, Adaptation, Physiological, Amino Acid Sequence, Fluorescence, Nuclear Envelope, Saccharomyces cerevisiae, Reproducibility of Results, Amino Acid Motifs, Nuclear Pore, Nuclear Pore Complex Proteins, Saccharomyces cerevisiae Proteins, Molecular Docking Simulation

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