Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9882291 | Archives of Biochemistry and Biophysics | 2005 | 12 Pages |
Abstract
Mastin is a tryptic peptidase secreted by canine mast cells. This work reveals that mastin is composed of catalytic domain singlets and disulfide-linked dimers. Monomers unite non-covalently to form tryptase-like tetramers, whereas dimers aggregate with monomers into larger clusters stabilized by hydrophobic contacts. Unlike tryptases, mastin resists inactivation by leech-derived tryptase inhibitor, indicating a smaller central cavity, as confirmed by structural models. Nonetheless, mastin is strongly gelatinolytic while not cleaving native collagen or casein, suggesting a preference for denatured proteins threaded into its central cavity. Phylogenetic analysis suggests that mammalian mastins shared more recent ancestors with soluble α/β/δ tryptases than with membrane-anchored γ-tryptases, and diverged more rapidly. We hypothesize that gelatinase activity and formation of inhibitor-resistant oligomers are ancestral characteristics shared by soluble tryptases and mastins, and that secreted mastin is a mini-proteasome-like complex that breaks down partially degraded proteins without causing bystander damage to intact, native proteins.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Wilfred W. Raymond, Christian P. Sommerhoff, George H. Caughey,