Abstract
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 RanBP2 structural modules. Some of these play a role in chaperoning the functional expression of opsin. RanBP2 localization at cytoplasmic fibrils emanating from the nuclear pore complex and interaction with the Ran-GTPase support also its role in nucleocytoplasmic transport processes. The degenerate nucleoporin repeat motifs FXFG, GLFG, and XXFG have been proposed to mediate the movement of nucleocytoplasmic transport factors. In particular, RanBP2 has been implicated in nuclear import processes. Here, we show the zinc fingers 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 for exportin-1 association with RanBP2. In contrast to Ran interaction with RanBP2-exportin-1 complex, exportin-1 binding to the zinc finger cluster domain 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, RanBP2 emerges as a key component of the nuclear export pathway.
Highlights
Protein machines are composed of assemblies of many distinct protein molecules [1]
Analysis of the size of PCR products (Fig. 1b) and nucleic acid sequence comparison of the bovine zinc finger cluster domain (ZnF) domain with the HeLa counterpart sequence showed that it contained only five out of the eight ZnF motifs previously reported in human RANBP2. (Fig. 2)
We investigated the behavior of Ran-GTPase in the formation of exportin-11⁄7ZnF complex in the presence and absence of Leptomycin B (LMB) and/or guanine nucleotides and the effect of LMB in the docking reaction of exportin-1 to the ZnF domain of Ran-binding protein 2 (RanBP2)
Summary
Protein machines are composed of assemblies of many distinct protein molecules [1]. Many are ubiquitous throughout cells, and emerging evidence shows that networks of intertwining protein machines underline many cellular processes. Whereas many of these protein-protein interactions occur in a stable fashion, others may be transient in nature This allows the fluid recruitment of substrates into higher order complexes and modulation of biological responses. The 19 S regulatory subunits of the proteasome associated and selectively in retinal tissue with the cyclophilin-like domain (CLD) of RanBP2 [2, 4]. To this end, we have proposed that the association of RanBP2 with the proteasome may lead to the processing of RanBP2 and production of at least another smaller RanBP2 isoform in retinal cells [2]. The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AJ133723
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
