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EAT-18 is an essential auxiliary protein interacting with the non-alpha nAChR subunit EAT-2 to form a functional receptor
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EAT-18 is an essential auxiliary protein interacting with the non-alpha nAChR subunit EAT-2 to form a functional receptor
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Journal Article
EAT-18 is an essential auxiliary protein interacting with the non-alpha nAChR subunit EAT-2 to form a functional receptor
2020
Overview
Nematode parasites infect approximately 1.5 billion people globally and are a significant public health concern. There is an accepted need for new, more effective anthelmintic drugs. Nicotinic acetylcholine receptors on parasite nerve and somatic muscle are targets of the cholinomimetic anthelmintics, while glutamate-gated chloride channels in the pharynx of the nematode are affected by the avermectins. Here we describe a novel nicotinic acetylcholine receptor on the nematode pharynx that is a potential new drug target. This homomeric receptor is comprised of five non-α EAT-2 subunits and is not sensitive to existing cholinomimetic anthelmintics. We found that EAT-18, a novel auxiliary subunit protein, is essential for functional expression of the receptor. EAT-18 directly interacts with the mature receptor, and different homologs alter the pharmacological properties. Thus we have described not only a novel potential drug target but also a new type of obligate auxiliary protein for nAChRs.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Acetylcholine receptors (nicotinic)
/ Animals
/ Antinematodal Agents - pharmacology
/ Caenorhabditis elegans - drug effects
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - metabolism
/ Caenorhabditis elegans Proteins - genetics
/ Caenorhabditis elegans Proteins - metabolism
/ Funding
/ Gene Expression Regulation - drug effects
/ Helminth Proteins - genetics
/ Helminth Proteins - metabolism
/ Homology
/ Ligands
/ Medicine and Health Sciences
/ Muscles
/ Novels
/ Pharynx
/ Proteins
/ Receptors, Nicotinic - genetics
/ Receptors, Nicotinic - metabolism
