Structure of the epididymal retinoic acid binding protein at 2.1 A resolution

Structure. 1993 Sep 15;1(1):7-18. doi: 10.1016/0969-2126(93)90004-z.


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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Computer Graphics
  • Crystallography, X-Ray
  • Epididymis / metabolism*
  • Ligands
  • Male
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Protein Conformation*
  • Protein Structure, Secondary*
  • Rats
  • Receptors, Retinoic Acid / chemistry*
  • Receptors, Retinoic Acid / metabolism
  • Sequence Homology, Amino Acid
  • Tretinoin / chemistry*
  • Tretinoin / metabolism


  • Ligands
  • Receptors, Retinoic Acid
  • Tretinoin