Structure of the epididymal retinoic acid binding protein at 2.1 A resolution.
BACKGROUND
Androgen-dependent proteins in the lumen of the epididymis are required for sperm maturation. One of these is a retinoic acid binding protein, E-RABP, which binds both all-trans and 9-cis retinoic acid. The other retinoid-binding proteins whose structures are known do not bind 9-cis retinoids.


RESULTS
We describe the X-ray structure determination of E-RABP with and without bound ligand. The ligand binds deep in the beta-barrel of the protein, the beta-ionone ring innermost. The binding site, like the ligand, is amphipathic and the deepest part of the cavity is formed by a ring of aromatic amino acids. The isoprene tail of all-trans retinoic acid is bound in a folded conformation which resembles that of the 9-cis isomer.


CONCLUSIONS
E-RABP achieves high-affinity binding of both all-trans and 9-cis isomers of retinoic acid by forcing the all-trans form to bind in a folded conformation. The RAR family of nuclear receptors for retinoic acid also binds both isomers, and their binding sites may therefore be similar.
Newcomer
M E
ME
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004822:Epididymis / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014212:Tretinoin / Q000737:chemistry* / Q000378:metabolism
D008024:Ligands; D018168:Receptors, Retinoic Acid; D014212:Tretinoin