The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1

The Ran-binding protein 2 (RanBP2) is a large scaffold cyclophilin-related protein expressed in photoreceptor cells. Red/green opsin, Ran-GTPase, and the 19 S regulatory complex of the proteasome associate with specific RanBP 2 structural modules. Some of these play a role in chaperoning the function al expression of opsin. RanBP2 localization at cytoplasmic fibrils emanatin g from the nuclear pore complex and interaction with the Ran GTPase support also its role in nucleocytoplasmic transport processes. The degenerate nuc leoporin repeat motifs FXFG, GLFG, and XXFG have been proposed to mediate t he movement of nucleocytoplasmic transport factors, In particular, RanBP2 h as been implicated in nuclear import processes, Here, we show the zinc fing ers of RanBP2 associate with high specificity to the nuclear export factor, exportin-1 (CRM1). The bovine RanBP2 transcript contained only five of the eight zinc fingers reported in the human counterpart and are sufficient fo r exportin-1 association with RanBP2. In contrast to Ran interaction with R anBP2-exportin-1 complex, exportin-1 binding to the zinc finger cluster dom ain of RanBP2 is insensitive to leptomycin B and nucleotide-bound state of Ran-GTPase. Our results indicate that the zinc finger-rich domain of RanBP2 constitutes a docking site for exportin-1 during nuclear export. Thus, Ran BP2 emerges as a key component of the nuclear export pathway.