Crystallographic studies on a family of cellular lipophilic transport proteins: Refinement of P2 myelin protein and the structure determination and refinement of cellular retinol-binding protein in complex with all-trans-retinol

Sandra W. Cowan, Uppsala Biomedicinska Centrum
Marcia E. Newcomer, Uppsala Biomedicinska Centrum
T. Alwyn Jones, Uppsala Biomedicinska Centrum

Abstract

P2 myelin protein (P2) and cellular retinol binding protein (CRBP) are members of a family of cellular lipophilic transport proteins. P2 has been refined at a resolution of 2.7 Å, and CRBP has been solved by molecular replacement and refined to a resolution of 2.1 Å. The members of this family form a compact three-dimensional structure built up from ten anti-parallel strands that fold to form an orthogonal barrel containing the ligand. In P2, the carboxylate group of an oleic acid ligand interacts with the side-chains of two arginine (106 and 126), and one tyrosine (128) residues. The ligand adopts a U-shaped conformation. In CRBP, the all-trans-retinol has a planar conformation with its alcohol group hydrogen bonding to the side-chain of glutamine 108 (equivalent to residue 106 in P2). The local interactions of glutamine 108 explain CRBP's preference for binding retinol rather than retinal. The side-chain of lysine 40 makes a close contact with the isoprene tail of the retinol. © 1993 Academic Press, Inc.