1. The molecular architecture of the nuclear basket.
- Author
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Singh, Digvijay, Soni, Neelesh, Hutchings, Joshua, Echeverria, Ignacia, Shaikh, Farhaz, Duquette, Madeleine, Suslov, Sergey, Li, Zhixun, van Eeuwen, Trevor, Molloy, Kelly, Shi, Yi, Wang, Junjie, Guo, Qiang, Chait, Brian T., Fernandez-Martinez, Javier, Rout, Michael P., Sali, Andrej, and Villa, Elizabeth
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NUCLEAR pore complex , *NUCLEAR transport , *NUCLEOCYTOPLASMIC interactions , *PROTEIN domains , *NUCLEOPORINS - 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. [Display omitted] • A stable basket is anchored by a hub of Nups into a double nuclear ring • Mlps/Tprs form struts; their N/C termini form a distal density that docks mRNA • A 20-nm exclusion zone around the basket suggests its role in chromatin organization • The stoichiometry of the outer rings is variable across and within species The elusive architecture of the nuclear basket reveals that a double ring is necessary to stabilize a hub of Nups from which the struts emanate. The basket's distal density contains the N/C termini of the strut-forming proteins that serve as a docking platform for cargo and nuclear periphery elements. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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