Cyclophilin-related protein RanBP2 acts as chaperone for red/green opsin

• Published in: Nature (London) 1996-10, Vol.383 (6601), p.637-640
• Main Authors: Ferreira, Paulo A, Nakayama, Tomoko A, Pak, William L, Travis, Gabriel H
• Format: Article
• Language: English
• Subjects: Amino Acid Isomerases - metabolism; Animals; Binding Sites; Biological and medical sciences; Carrier Proteins - metabolism; Cattle; Cellular biology; Chaperonins - metabolism; COS Cells; DNA-Binding Proteins - metabolism; Drosophila; Eye and associated structures. Visual pathways and centers. Vision; Eyes & eyesight; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Humans; letter; Molecular Chaperones; multidisciplinary; Nuclear Pore Complex Proteins; Nuclear Proteins - metabolism; Peptidylprolyl Isomerase; Photoreception; Protein Binding; Proteins; Recombinant Fusion Proteins - metabolism; Retina - metabolism; Rod Opsins - metabolism; Science; Science (multidisciplinary); Vertebrates; Vertebrates: nervous system and sense organs
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/383637a0

CYCLOPHILINS are ubiquitous and abundant proteins that exhibit peptidyl prolyl cis-trans isomerization (PPlase) activity in vitro 1,2 . Their functions in vivo , however, are not well understood. Two new retinal cyclophilin isoforms, types I and II, are highly expressed in cone photoreceptors of the vertebrate retina 3 . Type-II cyclophilin is identical to RanBP2, a large protein that binds the GTPase Ran 4,5 . Here we report that two contiguous domains in RanBP2, Ran-binding domain 4 (RBD4) and cyclophilin, act in concert as a chaperone for the opsin molecule of the red/green-sensitive visual pigment of a dichromatic vertebrate. In Drosophila , the cyclophilin NinaA 6,7 is expressed in all photoreceptors 8 and is required for the expression of only a subset of opsins 8,9 . The molecular basis of these photoreceptor class-specific effects and the functions of NinaA and other cyclophilins in vivo remain unclear 10 . Unlike NinaA, which forms a stable complex with opsin from retinular cells Rl–6 11 , we find that the cyclophilin domain of RanBP2 does not bind opsin directly; rather, it augments and stabilizes the interaction between red/green (R/G) opsin and the RBD4 domain. This involves a cyclophilin-mediated modification of R/G opsin, possibly involving proline isomerization. The RBD4–cyclophilin supradomain of RanBP2, therefore, is a form of vertebrate chaperone of defined substrate specificity, which may be involved in the processing and/or transport of long-wavelength opsin in cone photoreceptor cells.