Mastin is a gelatinolytic mast cell peptidase resembling a mini-proteasome

Arch Biochem Biophys. 2005 Mar 15;435(2):311-22. doi: 10.1016/j.abb.2004.12.025.

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 alpha/beta/delta tryptases than with membrane-anchored gamma-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caseins / metabolism
  • Catalytic Domain / drug effects
  • Collagen / metabolism
  • Dimerization
  • Dogs
  • Gelatin / metabolism*
  • Gene Library
  • Humans
  • Mast Cells / drug effects
  • Mast Cells / enzymology*
  • Mast Cells / metabolism
  • Models, Molecular*
  • Molecular Sequence Data
  • Phylogeny
  • Protease Inhibitors / pharmacology
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Endopeptidase Complex / metabolism*
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / drug effects
  • Serine Endopeptidases / metabolism*
  • Substrate Specificity

Substances

  • Caseins
  • Protease Inhibitors
  • Gelatin
  • Collagen
  • Serine Endopeptidases
  • Proteasome Endopeptidase Complex

Associated data

  • GENBANK/AY665677
  • GENBANK/AY665678