RETINOID SPECIFICITY OF INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN

Interphotoreceptor retinoid-binding protein (IRBP), the predominant pr otein in the interphotoreceptor matrix of retina, has been implicated in transfer of retinoids between retinal pigment epithelium and photor eceptor cells. In this work, the interactions of several retinoids wit h IRBP were studied in order to clarify whether the protein displays s pecificity toward particular forms of these ligands. The equilibrium d issociation constants of complexes of 11-cis- and all-trans-retinols a nd retinaldehydes with IRBP were measured. It was found that IRBP cont ains two binding sites for 11-cis-retinaldehyde and for all-trans-reti naldehyde and retinol. Binding affinities followed the order: 11-cis-r etinaldehyde > all-trans-retinol > all-trans-retinaldehyde > 11-cis-re tinol. The kinetic parameters of the dissociation of these retinoids f rom binding sites on IRBP were measured by monitoring the rate of tran sfer of the retinoids from IRBP to synthetic unilamellar vesicles. 11- cis-Retinaldehyde and all-trans-retinol were found to dissociate from the strong binding site of IRBP 3-4-fold slower than all-trans-retinal dehyde and 11-cis-retinol. The higher binding affinities and the slowe r rates of dissociation from IRBP displayed by 11-cis-retinaldehyde an d by all-trans-retinol correspond to the physiological need to shuttle these particular retinoids between pigment epithelium and photorecept or cells across the interphotoreceptor matrix as part of the visual cy cle.