New member of the trefoil factor family of proteins is an alpha-macroglobulin protease inhibitor.
The amino acid sequence of the monomeric alpha-macroglobulin (alphaM) 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 alphaM family of protein. The central portion of the frog monomeric alphaM contained Cys residues positioned analogously to the Cys residues in human alpha(2)-macroglobulin (alpha(2)M), known to be involved in disulfide bridges. Additionally, the frog monomeric alphaM contained six Cys residues in a approximately 60 residue COOH-terminal extension not present in previously characterized alphaMs. 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 Arg(675)-Lys(685) 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.
Thøgersen
Ida B
IB
Department of Molecular and Structural Biology, University of Arhus, Gustav Wieds Vej 10C, Aarhus, Denmark.
Hammes
Stephen R
SR
Rubenstein
David S
DS
Pizzo
Salvatore V
SV
Valnickova
Zuzana
Z
Enghild
Jan J
JJ
D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D010450:Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006133:Growth Substances / Q000737:chemistry* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011892:Rana catesbeiana; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification
D029845:Amphibian Proteins; D004791:Enzyme Inhibitors; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D011480:Protease Inhibitors; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D000511:alpha-Macroglobulins; D010450:Endopeptidases