A tetrameric acetylcholinesterase from the parasitic nematode Dictyocaulus viviparus associates with the vertebrate tail proteins PRiMA and ColQ.

Abstract

Dictyocaulus viviparus causes a serious lung disease of cattle. Similar to other parasitic nematodes, D. viviparus possesses several acetylcholinesterase (AChE) genes, one of which encodes a putative neuromuscular AChE, which contains a tryptophan (W) amphiphilic tetramerization (WAT) domain at its C-terminus. In the current study, we describe the biochemical characterization of a recombinant version of this WAT domain-containing AChE. To assess if the WAT domain is biologically functional, we investigated the association of the recombinant enzyme with the vertebrate tail proteins, proline-rich membrane anchor (PRiMA) and collagen Q (ColQ), as well as the synthetic polypeptide poly-l-proline. The results indicate that the recombinant enzyme hydrolyzes acetylthiocholine preferentially and exhibits inhibition by excess substrate, a characteristic of AChEs but not butyrylcholinesterases (BChEs). The enzyme is inhibited by the AChE inhibitor, BW284c51, but not by the BChE inhibitors, ethopropazine or iso-OMPA. The enzyme is able to assemble into monomeric (G(1)), dimeric (G(2)), and tetrameric (G(4)) globular forms and can also associate with PRiMA and ColQ, which contain proline-rich attachment domains (PRADs). This interaction is likely to be mediated via WAT-PRAD interactions, as the enzyme also assembles into tetramers with the synthetic polypeptide poly-l-proline. These interactions are typical of AChE(T) subunits. This is the first demonstration of an AChE(T) from a parasitic nematode that can assemble into heterologous forms with vertebrate proteins that anchor the enzyme in cholinergic synapses. We discuss the implications of our results for this particular host/parasite system and for the evolution of AChE.

• Authors: Leo Pezzementi, Eric Krejci, Arnaud Chatonnet, Murray E Selkirk, Jacqueline B Matthews
• Journal: Molecular and biochemical parasitology (Mol Biochem Parasitol) Vol. 181 Issue 1 Pg. 40-8 (Jan 2012) ISSN: 1872-9428 [Electronic] Netherlands
• PMID: 22027027 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Nerve Tissue Proteins
• Peptides
• Recombinant Proteins
• polyproline
• Collagen
• Acetylcholinesterase

Topics

• Acetylcholinesterase (chemistry, genetics, isolation & purification, metabolism)
• Amino Acid Sequence
• Animals
• Collagen (metabolism)
• Dictyocaulus (enzymology)
• Molecular Sequence Data
• Nerve Tissue Proteins (metabolism)
• Peptides (metabolism)
• Phylogeny
• Protein Binding
• Protein Multimerization
• Protein Structure, Tertiary
• Recombinant Proteins (chemistry, genetics, metabolism)
• Sequence Homology, Amino Acid