THE CYCLOPHILIN-LIKE DOMAIN MEDIATES THE ASSOCIATION OF RAN-BINDING PROTEIN-2 WITH SUBUNITS OF THE 19 S REGULATORY COMPLEX OF THE PROTEASOME

The combination of the Ran-binding domain 4 and cyclophilin domains of Ran-binding protein 2 selectively associate with a subset of G protei n-coupled receptors, red/green opsins, upon cis-trans prolyl isomerase -dependent and direct modification of opsin followed by association of the modified opsin isoform to Ran-binding domain 4. This effect enhan ces in vivo the production of functional receptor and generates an ops in isoform with no propensity to self-aggregate in vitro. We now show that another domain of Ran-binding protein 2, cyclophilin-like domain, specifically associates with the 112-kDa subunit, P112, and other sub units of the 19 S regulatory complex of the 26 S proteasome in the neu roretina. This association possibly mediates Ran-binding protein 2 lim ited proteolysis into a smaller and stable isoform. Also, the interact ion of Ran-binding protein 2 with P112 regulatory subunit of the 26 S proteasome involves still another protein, a putative kinesin-like pro tein. Our results indicate that Ran-binding protein 2 is a key compone nt of a macro-assembly complex selectively linking protein biogenesis with the proteasome pathway and, thus, with potential implications for the presentation of misfolded and ubiquitin-like modified proteins to this proteolytic machinery.