Secretion of α2-Plasmin Inhibitor Is Impaired by Amino Acid Deletion in a Small Region of the Molecule

Abstract

α2-Plasmin inhibitor (α₂PI) deficiency Okinawa results from defective secretion of the inhibitor from the liver and appears to be a direct consequence of the deletion of Glu¹³⁷ in the amino acid sequence of α₂PI. To examine the effects of replacing the amino acid occupying position 137 or deleting its neighboring amino acid on α₂PI secretion, we used oligonucleotide-directed mutagenesis of α₂PI cDNA to change the codon specifying Glu¹³⁷ or delete a codon specifying its neighboring amino acid. The effects were determined by pulse-chase experiments and by enzyme-linked immunosorbent assay of media from transiently transfected COS-7 cells. Replacement of Glu¹³⁷ with an amino acid other than Cys had little effect on α₂PI secretion. In contrast, deletion of an amino acid in a regio spanning a sequence of less than 30 amino acids including positions 127 and 137 severely impaired the secretion. The results suggest that structural integrity of the region, ratherthan its component amino acids, is important for the intracellular transport and secretion of α₂PI.