The binding protein of corticotropin-releasing factor: Ligand-binding site and subunit structure

AUTOR(ES)

Jahn, Olaf

FONTE

National Academy of Sciences

RESUMO

Corticotropin-releasing factor (CRF), recognized as an important stress factor, binds to a CRF receptor and a CRF-binding protein (CRFBP) that represents a reservoir of endogenous CRF. Although CRFBP was observed to dimerize, at least in part, the ligand was found to be exclusively bound to the monomer—as indicated by photoaffinity labeling. We localized the CRF binding site by using photoaffinity labeling in combination with different mass spectrometric techniques. The amino acid residues Arg-23 and Arg-36 of CRFBP were identified as the sites of photoincorporation of monofunctional and bifunctional photoprobes designed on the basis of the amino acid sequence of human/rat CRF6–33. It was, therefore, concluded that the sequence of amino acid residues 23–36 of CRFBP is involved in ligand binding. Our data are in support of an antiparallel alignment of the photoprobe with the amino acid residues 23–36 of the CRFBP monomer.

Documentos Relacionados

• Mapping of the ligand-selective domain of the Xenopus laevis corticotropin-releasing factor receptor 1: Implications for the ligand-binding site
• Primary structure of corticotropin-releasing factor from ovine hypothalamus.
• Characterization of rat hypothalamic corticotropin-releasing factor.
• Immunoreactive corticotropin-releasing factor in human plasma.
• Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal