Structures of cellular retinoic acid binding proteins I and II in complex with synthetic retinoids

Retinoids play important roles in diverse cellular processes including grow th, cell differentiation and vision. Many natural and synthetic retinoids a re used as drugs in dermatology and oncology. A large amount of data has be en accumulated on the cellular activity of different synthetic retinoids. T hey are stabilized and transported inside the cell cytoplasm by binding and transport proteins,such as cellular retinol-binding proteins and cellular retinoic acid binding proteins (CRABPs). The structures of human CRABP II i n complex with two different synthetic retinoids, Ro13-6307 and Ro12-7310 ( at 2.1 and 2.0 Angstrom resolution, respectively) and of bovine CRABP I in complex with a retinobenzoic acid, Am80 (at 2.8 Angstrom resolution) are de scribed. The binding affinities of human CRABP I and II for the retinoids s tudied here have been determined. All these compounds have comparable bindi ng affinities (nanomolar range) for both CRABPs. Apart from the particular interactions of the carboxylate group of the retinoids with specific protei n groups, each structure reveals characteristic interactions. Studying the atomic details of the interaction of retinoids with retinoid-binding protei ns facilitates the understanding of the kinetics of retinoid trafficking in side the cytoplasm.