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New member of the trefoil factor family of proteins is an α-macroglobulin protease inhibitor

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  • Ida B. Thøgersen
  • Stephen R. Hammes, University of Texas Southwestern Medical Center
  • ,
  • David S. Rubenstein, University of North Carolina School of Medicine
  • ,
  • Salvatore V. Pizzo, Duke University Medical Center
  • ,
  • Zuzana Valnickova, Aarhus University
  • ,
  • Jan J. Enghild
  • Department of Molecular Biology

The amino acid sequence of the monomeric α-macroglobulin (αM) from the American bullfrog, Rana catesbiana, was determined. The mature protein consisted of 1469 amino acid residues and shared sequence identity with other members of the αM family of protein. The central portion of the frog monomeric αM contained Cys residues positioned analogously to the Cys residues in human α2-macroglobulin (α2M), known to be involved in disulfide bridges. Additionally, the frog monomeric αM contained six Cys residues in a ∼60 residue COOH-terminal extension not present in previously characterized αMs. The spacing of the Cys residues and the overall sequence identity of this COOH-terminal extension were consistent with a trefoil motif. This is the first time a member of the trefoil factor family has been identified in the circulatory system. The "bait region" was located between Arg675-Lys685 and contained mainly basic amino acid residues. The COOH-terminal receptor-binding domain was not exposed prior to proteolysis of this highly susceptible region. The proximity of the receptor-binding and trefoil domains implied that the trefoil domain is similarly concealed before bait region cleavage.

Original languageEnglish
JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Pages (from-to)131-139
Number of pages9
Publication statusPublished - 29 Jul 2002

    Research areas

  • Protease, Trefoil factor, α-Macroglobulin

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