Cleavage of hemoglobin by hookworm cathespin D aspartic proteases and its potential contribution to host specificity

Williamson, Angela L., Brindley, Paul J., Abbenante, Giovanni, Prociv, Paul, Berry, Colin, Girdwood, Karen, Pritchard, David I., Fairlie, David P., Hotez, Peter J., Dalton, John P. and Loukas, Alex C. (2002) Cleavage of hemoglobin by hookworm cathespin D aspartic proteases and its potential contribution to host specificity. The FASEB Journal, 16 10: 1458-1460. doi:10.1096/fj.02-0181fje


Author Williamson, Angela L.
Brindley, Paul J.
Abbenante, Giovanni
Prociv, Paul
Berry, Colin
Girdwood, Karen
Pritchard, David I.
Fairlie, David P.
Hotez, Peter J.
Dalton, John P.
Loukas, Alex C.
Title Cleavage of hemoglobin by hookworm cathespin D aspartic proteases and its potential contribution to host specificity
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2002-08-01
Year available 2002
Sub-type Article (original research)
DOI 10.1096/fj.02-0181fje
Open Access Status DOI
Volume 16
Issue 10
Start page 1458
End page 1460
Total pages 3
Place of publication USA
Publisher Federation of American Societies for Experimental Biology
Language eng
Subject C1
320405 Medical Parasitology
730101 Infectious diseases
Abstract Hookworms routinely reach the gut of nonpermissive hosts but fail to successfully feed, develop, and reproduce. To investigate the effects of host-parasite coevolution on the ability of hookworms to feed in nonpermissive hosts, we cloned and expressed aspartic proteases from canine and human hookworms. We show here that a cathepsin D-like protease from the canine hookworm Ancylosotoma caninum (Ac-APR-1) and the orthologous protease from the human hookworm Necator americanus (Na-APR-1) are expressed in the gut and probably exert their proteolytic activity extracellularly. Both proteases were detected immunologically and enzymatically in somatic extracts of adult worms. The two proteases were expressed in baculovirus, and both cleaved human and dog hemoglobin (Hb) in vitro. Each protease digested Hb from its permissive host between twofold (whole molecule) and sixfold (synthetic peptides) more efficiently than Hb from the nonpermissive host, despite the two proteases' having identical residues lining their active site clefts. Furthermore, both proteases cleaved Hb at numerous distinct sites and showed different substrate preferences. The findings suggest that the paradigm of matching the molecular structure of the food source within a host to the molecular structure of the catabolic proteases of the parasite is an important contributing factor for host-parasite compatibility and host species range.
Keyword Biochemistry & Molecular Biology
Biology
Cell Biology
Parasite
Ancylostoma Caninum
Necator Americanus
Nematode
Human Eosinophilic Enteritis
Adult Haemonchus-contortus
Blood-feeding Parasites
Ancylostoma-caninum
Plasmodium-falciparum
Caenorhabditis-elegans
In-vivo
Degradation
Infection
Identification
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Wed, 15 Aug 2007, 03:22:36 EST