Structural and Functional Analysis of the C-Terminal Domain of Nup358/RanBP2

The nuclear pore complex is the sole mediator of bidirectional transport between the nucleus and cytoplasm. Nup358 is a metazoan-specific nucleoporin that localizes to the cytoplasmic filaments and provides several binding sites for the mobile nucleocytoplasmic transport machinery. Here we present the crystal structure of the C-terminal domain (CTD) of Nup358 at 1.75 Å resolution. The structure reveals that the CTD adopts a cyclophilin-like fold with a non-canonical active-site configuration. We determined biochemically that the CTD possesses weak peptidyl-prolyl isomerase activity and show that the active-site cavity mediates a weak association with the human immunodeficiency virus-1 capsid protein, supporting its role in viral infection. Overall, the surface is evolutionarily conserved, suggesting that the CTD serves as a protein–protein interaction platform. However, we demonstrate that the CTD is dispensable for nuclear envelope localization of Nup358, suggesting that the CTD does not interact with other nucleoporins.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (401 K)Download as PowerPoint slideHighlights► Crystal structure of the CTD of Nup358. ► Nup358 CTD has peptidyl-prolyl isomerase activity. ► Nup358 CTD has weak binding affinity for human immunodeficiency virus-1 capsid protein. ► Nup358 CTD is dispensable for nuclear envelope localization.