Processing of the human heparanase precursor and evidence that the active enzyme is a heterodimer

Human platelet heparanase has been purified to homogeneity and shown to con sist of two, non-covalently associated polypeptide chains of molecular mass es 50 and 8 kDa. Protein sequencing provided the basis far determination of the full-length cDNA for this novel protein. Based upon this information a nd results from protein analysis and mass spectrometry, we propose a scheme to define the structural organization of heparanase in relation to its pre cursor forms, proheparanase and pre-proheparanase. The 8- and 50-kDa chains which make up the active enzyme reside, respectively, at the NH2- and COOH -terminal regions of the inactive: precursor, proheparanase. The heparanase heterodimer is produced by excision and loss of an internal linking segmen t. This paper is the first to suggest that human heparanase is a two-chain enzyme.