Molecular cloning and demonstration of an aminopeptidase activity in a filarial nematode glycoprotein

Harnett, William; Houston, Katrina M.; Tate, Rothwelle J.; Gárate, Teresa; Apfel, Heiko; Adam, Ralf; Haslam, Stuart M.; Panico, Maria; Paxton, Thanai; Dell, Anne; Morris, Howard R.; Brzeski, Henry

doi:10.1016/s0166-6851(99)00113-9

Cited by 28 publications

(21 citation statements)

References 36 publications

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“…Sequence alignment suggests that these proteins belong to the same family and possibly have related functions and structures. Regarding function, and consistent with the sequence homologies, in vitro analyses employing synthetic substrates suggest that ES-62 may possess aminopeptidase activity [11].…”

Section: Es-62-biological and Structural Aspectssupporting

confidence: 59%

“…ES-62 was initially cloned from an adult female A. viteae cDNA library [11]. cDNA sequence analysis of the clone in combination with N-terminal amino acid sequencing and Q-TOF sequencing of tryptic peptides of native ES-62 revealed the secreted form of the molecule to consist of 474 amino acids with a molecular mass of 52.8 kDa and an isoelectric point of 5.96 [11].…”

Section: Es-62-biological and Structural Aspectsmentioning

confidence: 99%

“…cDNA sequence analysis of the clone in combination with N-terminal amino acid sequencing and Q-TOF sequencing of tryptic peptides of native ES-62 revealed the secreted form of the molecule to consist of 474 amino acids with a molecular mass of 52.8 kDa and an isoelectric point of 5.96 [11]. Analysis of the protein coding sequence using PRINTS/PROSITE scanner for conserved motifs revealed the presence of four potential N-linked glycosylation sites [11]. It is likely that at least three of these is utilised as ES-62 has been shown by fast atom bombardment mass spectroscopy (FABMS) to contain three distinct types of N-glycan [12].…”

Section: Es-62-biological and Structural Aspectsmentioning

confidence: 99%

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ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential

Harnett¹,

McInnes²,

Harnett³

2004

Immunology Letters

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Section: Es-62-biological and Structural Aspectssupporting

confidence: 59%

Section: Es-62-biological and Structural Aspectsmentioning

confidence: 99%

Section: Es-62-biological and Structural Aspectsmentioning

confidence: 99%

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ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential

Harnett¹,

McInnes²,

Harnett³

2004

Immunology Letters

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“…Additionally, L. sigmodontis homologs of Av33 and ES-62, proteins known to be abundant in the ESP from adult females of other filarial species, were identified. Av33 is similar to an aspartate protease inhibitor from A. suum (47), whereas ES-62 is a secreted leucyl aminopeptidase (48). Three of the gAF ESP proteins had putative lipid-binding regions: ML-domain proteins have been reported to interact with cholesterol and lipid A (49, 50), the conserved filarial antigen Ov16 has a putative phosphatidylethanolamine-binding domain (51), and a novel and highly abundant vitellogenin (nLs_07321) contained an amino-terminal lipid transport domain.…”

Section: Distribution Of Proteins In Esp Across Parasite Lifecyclementioning

confidence: 99%

Comparative Analysis of the Secretome from a Model Filarial Nematode (Litomosoides sigmodontis) Reveals Maximal Diversity in Gravid Female Parasites

Armstrong

Babayan

Lhermitte-Vallarino

et al. 2014

Molecular & Cellular Proteomics

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Filarial nematodes (superfamily Filarioidea) are responsible for an annual global health burden of ϳ6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. No vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained by the inability of the human-parasitic species to complete their lifecycles in laboratory mice. However, the rodent filaria Litomosoides sigmodontis has become a popular experimental model, as BALB/c mice are fully permissive for its development and reproduction. Here, we provide a comprehensive analysis of excretory-secretory products from L. sigmodontis across five lifecycle stages and identifications of host proteins associated with first-stage larvae (microfilariae) in the blood. Applying intensity-based quantification, we determined the abundance of 302 unique excretory-secretory proteins, of which 64.6% were present in quantifiable amounts only from gravid adult female nematodes. This lifecycle stage, together with immature microfilariae, released four proteins that have not previously been evaluated as vaccine candidates: a predicted 28.5 kDa filaria-specific protein, a zonadhesin and SCO-spondin-like protein, a vitellogenin, and a protein containing six metridin-like ShK toxin domains. Female nematodes also released two proteins derived from the obligate Wolbachia symbiont. Notably, excretory-secretory products from all parasite stages contained several uncharacterized members of the transthyretin-like protein family. Furthermore, biotin labeling revealed that redox proteins and enzymes involved in purinergic signaling were enriched on the adult nematode cuticle. Comparison of the L. sigmodontis adult secretome with that of the humaninfective filarial nematode Brugia malayi (reported previously in three independent published studies) identified differences that suggest a considerable underlying diversity of potential immunomodulators. The molecules identified in L. sigmodontis excretory-secretory products show promise not only for vaccination against filarial infections, but for the amelioration of allergy and autoimmune diseases. Molecular & Cellular

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“…We have previously described the presence of AREs in 2 out of 3 cDNA clones of ES-62 obtained from a female adult A. viteae cDNA library (Harnett et al 1999). Specifically, these clones were 77 .…”

Section: Discussionmentioning

confidence: 99%

Stage-specific and species-specific differences in the production of the mRNA and protein for the filarial nematode secreted product, ES-62

et al. 2004

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Previous studies have shown that the secreted phosphorylcholine-containing glycoprotein of filarial nematodes, ES-62, is only present in the post-infective life-cycle stages, but that the mRNA is transcribed throughout the worm's life-cycle. The aim of this current study was to investigate whether the presence or absence of protein expression simply reflects differences in mRNA abundance. To this end, we investigated the relative abundance of ES-62 using TaqMan real time RT-PCR, in different life-cycle stages of 2 model filarial nematode parasites, Acanthocheilonema viteae and Brugia pahangi. For B. pahangi, microfilariae, infective larvae and adult worms were each found to have approximately similar levels of ES-62 mRNA. However, the corresponding stages of A. viteae differed greatly from each other with a pattern of increased mRNA production with maturation. As a rule A. viteae had higher levels of ES-62 mRNA than B. pahangi, and this was particularly noticeable in the adult stage where the difference was approximately 3500-fold higher. However, this significant difference in mRNA abundance was not reflected in the quantity of ES-62 protein secreted by the adult worms of each species, as A. viteae only secreted approximately 3 times as much ES-62 as B. pahangi. Thus, overall, the results obtained from this study indicate that ES-62 protein production does not solely reflect mRNA levels, and also suggest that the 2 nematodes may employ different mechanisms for regulating protein production.

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Molecular cloning and demonstration of an aminopeptidase activity in a filarial nematode glycoprotein

Cited by 28 publications

References 36 publications

ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential

ES-62, a filarial nematode-derived immunomodulator with anti-inflammatory potential

Comparative Analysis of the Secretome from a Model Filarial Nematode (Litomosoides sigmodontis) Reveals Maximal Diversity in Gravid Female Parasites

Stage-specific and species-specific differences in the production of the mRNA and protein for the filarial nematode secreted product, ES-62

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