The molecular architecture of the nuclear basket
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.
Authors
- Zhixun Li (ORCID: https://orcid.org/0000-0002-7014-3635)
- Kelly R. Molloy (ORCID: https://orcid.org/0009-0006-3142-4481)
- Joshua Hutchings (ORCID: https://orcid.org/0000-0001-6841-8583)
- Neelesh Soni (ORCID: https://orcid.org/0000-0002-9333-7491)
- Andrej Săli (ORCID: https://orcid.org/0000-0003-0435-6197)
- Javier Fernández-Martı́nez (ORCID: https://orcid.org/0000-0003-0567-498X)
- Yi Shi (ORCID: https://orcid.org/0000-0002-2761-8324)
- Digvijay Singh (ORCID: https://orcid.org/0000-0002-7411-4436)
- Michael P. Rout (ORCID: https://orcid.org/0000-0003-2010-706X)
- Madeleine Duquette (ORCID: https://orcid.org/0009-0001-4737-542X)
- Ignacia Echeverria (ORCID: https://orcid.org/0000-0003-4717-1467)
- Trevor van Eeuwen (ORCID: https://orcid.org/0000-0003-0549-1702)
- Farhaz Shaikh (ORCID: https://orcid.org/0009-0002-0452-5675)
- Brian T. Chait (ORCID: https://orcid.org/0000-0003-3524-557X)
- Elizabeth Villa (ORCID: https://orcid.org/0000-0003-4677-9809)
- Sergey Suslov (ORCID: https://orcid.org/0000-0002-2332-1662)
- Junjie Wang (ORCID: https://orcid.org/0000-0002-6169-8145)
- Qiang Guo (ORCID: https://orcid.org/0000-0003-3520-5439)
Institutions
- QB3 (US)
- Ikerbasque (ES)
- Howard Hughes Medical Institute (US)
- University of the Basque Country (ES)
- University of California, San Francisco (US)
- Peking University (CN)
- University of California San Diego (US)
- Quantitative BioSciences (US)
- Instituto Biofisika (ES)
- Center for Life Sciences (CN)
- Rockefeller University (US)
Publication Details
- Journal
- Cell
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1016/j.cell.2024.07.020
- Citations
- 69
- Primary Topic
- Nuclear Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 16.13
Funders
- National Science Foundation
- Damon Runyon Cancer Research Foundation
- Agouron Institute
- National Institutes of Health
- University of California, San Diego