ESSENTIAL DYNAMICS OF THE CELLULAR RETINOL-BINDING PROTEIN - EVIDENCEFOR LIGAND-INDUCED CONFORMATIONAL-CHANGES

The cellular retinol-binding protein (CRBP) is an intracellular retino l carrier protein belonging to a family of hydrophobic ligand-binding proteins, It transports retinol to specific locations in the cell wher e, for instance, it is esterified for storage, Recently solved crystal lographic structures of CRBP homologues with and without bound ligand do not provide evidence for a ligand-induced conformational change, Ho wever, it has been shown that there is a difference in binding of holo -CRBP and apo-CRBP to lecithin-retinol acyltransferase, Moreover, prot eolysis of holo-CRBP and apo-CRBP yields different products, indicatin g a difference in structure or dynamics between the two forms, Here, w e present the results of molecular dynamics simulations of holo-CRBP a nd apo-CRBP, The simulations show a significant difference in conforma tion, in agreement with experimental results, The essential dynamics m ethod was used to study differences in dynamics between the apo and ho le forms of CRBP, and showed inhibition of essential motions upon liga nd binding, It also revealed large correlated motions of retinol with regions of the protein, pointing to a possible retinol entry/exit site .