Molecular characterization of a family of metalloendopeptidases from the intestinal brush border of Haemonchus contortus
| Autor: | S. K. Smith, Philip Skuce, W. D. Smith, George F.J. Newlands, D. Pettit, Alasdair J. Nisbet, Diane L. Redmond |
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| Rok vydání: | 2006 |
| Předmět: |
Signal peptide
Proteomics medicine.medical_treatment Molecular Sequence Data Antibodies Helminth Glycoprotein complex Endopeptidases medicine Animals Aspartic Acid Endopeptidases Humans Protease Inhibitors Amino Acid Sequence Cloning Molecular Integral membrane protein Peptide sequence chemistry.chemical_classification Protease Membrane Glycoproteins biology Reverse Transcriptase Polymerase Chain Reaction Metalloendopeptidases Helminth Proteins Hydrogen-Ion Concentration biology.organism_classification Protein Structure Tertiary Infectious Diseases chemistry Biochemistry Larva Metalloendopeptidase Animal Science and Zoology Parasitology Electrophoresis Polyacrylamide Gel Haemonchus Glycoprotein Sequence Alignment Haemonchus contortus |
| Zdroj: | Parasitology. 133(Pt 3) |
| ISSN: | 0031-1820 |
| Popis: | Substantial protection against the economically important parasitic nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of the worm (H-gal-GP). Previous studies showed that one of the major components of H-gal-GP is a family of at least 4 zinc metalloendopeptidases, designated MEPs 1–4. This paper describes aspects of the molecular architecture of this protease family, including the proteomic analysis of the MEP fraction of the H-gal-GP complex. These enzymes belong to the M13 zinc metalloendopeptidase family (EC 3.4.24.11), also known as neutral endopeptidases or neprilysins. The sequences of MEPs 1 and 3 suggested a typical Type II integral membrane protein structure, whilst MEPs 2 and 4 had putative cleavable signal peptides, typical of secreted proteins. Proteomic analysis of H-gal-GP indicated that the extracellular domain of all 4 MEPs had been cleaved close to the transmembrane region/signal peptide with additional cleavage sites mid-way along the polypeptide. MEP3 was present as a homo-dimer in H-gal-GP, whereas MEP1 or MEP2 formed hetero-dimers with MEP4. It was found that expression of MEP3 was confined to developing 4th-stage larvae and to adult worms, the stages of Haemonchus which feed on blood. MEP-like activity was detected in the H-gal-GP complex over a broad pH range (5–9). Since all 4 MEPs must share a similar microenvironment in the complex, this suggests that each might have a different substrate specificity. |
| Databáze: | OpenAIRE |
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