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 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.
Singh
B B
BB
Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Patel
H H
HH
Roepman
R
R
Schick
D
D
Ferreira
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D028884:Karyopherins; D051379:Mice; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D012172:Retinaldehyde / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D016335:Zinc Fingers; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004492:Edetic Acid; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012172:Retinaldehyde; D015032:Zinc; D000097606:Exportin 1 Protein; C094493:ran-binding protein 2; C038753:leptomycin B