Schistosome elastases: biological importance, structure, function and stage-specific expression.
Larval schistosomes (Digenea: Trematoda) invade their definitive host by directly penetrating the skin. During the process they secrete a number of macromolecules, ostensibly to facilitate their entry. Among these we have identified and characterized a dominant proteolytic species: a serine protease capable of fragmenting keratin, types IV and VIII collagen, proteoglycan, fibronectin, laminin, and elastin. The enzyme exhibits the specificity characteristic of elastases, has a molecular mass of 30,000 Da and pI of 7.8, and is potently immunogenic in its native form. Specificity of the active site has been analysed, tetrapeptides having large hydrophobic or aromatic amino acids at size P1 serving as best substrates. The amino terminal 20 amino acids of the mature enzyme have been sequenced and the information derived has been used to construct an oligonucleotide (22-mer) complement of its corresponding mRNA. The latter has been used to establish, by Northern analysis, that expression of the enzyme is stage specific (differing in this respect from most schistosome immunogens), and under transcriptional control. Transcripts are encoded by a multigene family. Several cDNAs hybridizing to the oligonucleotide have been isolated, subcloned into bacteriophage M-13, and sequenced by the di-deoxy method. It is our expectation that this line of investigation will lead towards: (i) an anti-infection vaccine; (ii) a means for chemically preventing infection (using enzyme inhibitors), and/or (iii) a rapid diagnostic assay of prepatent infection.
Newport
G
G
University of California Naval Biosciences Laboratory Naval Supply Center, Oakland, CA 94625.
McKerrow
J
J
Hedstrom
R
R
Culpepper
J
J
McGarrigle
L
L
Agabian
N
N
D000595:Amino Acid Sequence; D000818:Animals; D005796:Genes; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000235:genetics / Q000378:metabolism*; D012547:Schistosoma / Q000201:enzymology* / Q000235:genetics
D010196:Pancreatic Elastase