bioRxiv. 2024 Mar 28. pii: 2024.03.27.587068. [Epub ahead of print]
Digvijay Singh,
Neelesh Soni,
Joshua Hutchings,
Ignacia Echeverria,
Farhaz Shaikh,
Madeleine Duquette,
Sergey Suslov,
Zhixun Li,
Trevor van Eeuwen,
Kelly Molloy,
Yi Shi,
Junjie Wang,
Qiang Guo,
Brian T Chait,
Javier Fernandez-Martinez,
Michael P Rout,
Andrej Sali,
Elizabeth Villa.
The nuclear pore complex (NPC) is the sole mediator of nucle-ocytoplasmic 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 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.