Proteinase-sensitive regions in the heavy chain of low molecular weight kininogen map to the inter-domain junctions.
Low molecular weight kininogen from human plasma was subjected to limited proteolysis with trypsin, chymotrypsin, elastase, and bromelain, and the resulting fragments of 20,000 or 40,000 Da were isolated. Amino-terminal sequence analysis of the fragments disclosed for the various proteinases eight independent cleavage sites distinct from the typical kallikrein cleavage sites flanking the kinin region. All the identified cleavage sites cluster in two stretches of 11-12 residues of the kininogen heavy chain. These short segments represent the primary attack sites for proteinases ("proteinase-sensitive regions") in the heavy chain portion of human low molecular weight kininogen. The amino acid sequences of the two proteinase-sensitive regions are mutually homologous; they are further characterized by the presence of a single copy each of the consensus tetrapeptide Cys-X-Gly-Cys known to form a narrow disulfide loop (Kellermann, J., Thelen, C., Lottspeich, F., Henschen, A., Vogel, R., and Müller-Esterl, W. (1987) Biochem. J. 247, 15-21). The proteinase-sensitive regions are located at the junctions of the three cystatin-like domains constituting the kininogen heavy chain. Proteolytic cleavage at the sensitive regions dissects the kininogen heavy chain and releases single domains of 20,000 Da and combined domains of 40,000 Da which can function as cysteine proteinase inhibitors. The presence of kininogen heavy chain domains in plasma samples under pathologic conditions suggests that cleavage of the proteinase-sensitive regions might also occur in vivo.
D000595:Amino Acid Sequence; D001665:Binding Sites; D001963:Bromelains / Q000378:metabolism; D002846:Chromatography, Affinity; D002918:Chymotrypsin / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007118:Immunoassay; D007700:Kinetics; D007704:Kininogens / Q000097:blood / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000378:metabolism; D010206:Papain / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
D007704:Kininogens; D010446:Peptide Fragments; D001963:Bromelains; D010447:Peptide Hydrolases; D002918:Chymotrypsin; D010196:Pancreatic Elastase; D014357:Trypsin; D010206:Papain