Cloning, structure, and expression of a rat binding protein for polychlorinated biphenyls. Homology to the hormonally regulated progesterone-binding protein uteroglobin.

Abstract

Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. Here, we report the isolation of a cDNA encoding the rat lung PCB-binding protein. The identity of the PCB-binding protein is supported by expression of the cDNA in Cos-1 cells where the homogenates from transfected cells show specific binding of 4,4'-bis([ 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, a high affinity ligand for the PCB-binding protein. Also a monospecific antiserum to the PCB-binding protein recognizes a 13-kDa protein in the homogenates of transfected cells but not in the corresponding fraction of mock-transfected cells. Northern blot analysis of total RNA from different rat tissues demonstrates that the cDNA detects a approximately 600-base pair mRNA which appears to be solely expressed in lung. Interestingly, DNA sequence analysis and prediction of the amino acid sequence reveals that the PCB-binding protein shares 53% positional amino acid identity with uteroglobin, a progesterone-binding protein found in rabbit uterus and lung. Furthermore, amino acids shown by x-ray crystallography to delineate the central cavity of uteroglobin, which fits progesterone, are highly conserved in the two proteins.