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The molecular architecture of the nuclear basket

Affiliations
  • 1School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • 2Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 3Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 4State Key Laboratory of Protein and Plant Gene Research, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing 100871, P.R. China.
  • 5Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
  • 6Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
  • 7Laboratory 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. Electronic address: javier.fernandezma@ehu.eus.
  • 8Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: rout@rockefeller.edu.
  • 9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, 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. Electronic address: sali@salilab.org.
  • 10School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: evilla@ucsd.edu.

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August 10, 2024

Abstract

The nuclear pore complex (NPC) is the sole mediator of nucleocytoplasmic transport. Despite great advances in understanding its conserved core architecture, the peripheral regions can exhibit considerable variation within and between species. One such structure is the cage-like nuclear basket. Despite its crucial roles in mRNA surveillance and chromatin organization, an architectural understanding has remained elusive. Using in-cell cryo-electron tomography and subtomogram analysis, we explored the NPC’s structural variations and the nuclear basket across fungi (yeast; S. cerevisiae), mammals (mouse; M. musculus), and protozoa (T. gondii). Using integrative structural modeling, we computed a model of the basket in yeast and mammals that revealed how a hub of nucleoporins (Nups) in the nuclear ring binds to basket-forming Mlp/Tpr proteins: the coiled-coil domains of Mlp/Tpr form the struts of the basket, while their unstructured termini constitute the basket distal densities, which potentially serve as a docking site for mRNA preprocessing before nucleocytoplasmic transport.

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