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

Nature. 1996 Oct 17;383(6601):637-40. doi: 10.1038/383637a0.


Cyclophilins are ubiquitous and abundant proteins that exhibit peptidyl prolyl cis-trans isomerization (PPlase) activity in vitro. 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. Type-II cyclophilin is identical to RanBP2, a large protein that binds the GTPase Ran. 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 is expressed in all photoreceptors and is required for the expression of only a subset of opsins. The molecular basis of these photoreceptor class-specific effects and the functions of NinaA and other cyclophilins in vivo remain unclear. Unlike NinaA, which forms a stable complex with opsin from retinular cells R1-6, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Isomerases / metabolism*
  • Animals
  • Binding Sites
  • COS Cells
  • Carrier Proteins / metabolism*
  • Cattle
  • Chaperonins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Drosophila
  • Humans
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins*
  • Nuclear Proteins / metabolism*
  • Peptidylprolyl Isomerase
  • Protein Binding
  • Recombinant Fusion Proteins / metabolism
  • Retina / metabolism
  • Rod Opsins / metabolism*


  • Carrier Proteins
  • DNA-Binding Proteins
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Rod Opsins
  • long-wavelength opsin
  • middle-wavelength opsin
  • ran-binding protein 2
  • Chaperonins
  • Amino Acid Isomerases
  • Peptidylprolyl Isomerase