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.

中文翻译：

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EAT-18是与非αnAChR亚基EAT-2相互作用形成功能性受体的必需辅助蛋白。

线虫寄生虫感染了全球约15亿人，是一个重大的公共卫生问题。人们普遍需要新的，更有效的驱虫药。寄生虫神经和体细胞上的烟碱乙酰胆碱受体是拟蠕虫驱虫药的靶标，而线虫咽部的谷氨酸门控氯离子通道受阿维菌素的影响。在这里，我们描述了线虫咽上的一种新型烟碱乙酰胆碱受体，它是潜在的新药靶标。该同聚受体由五个非αEAT-2亚基组成，并且对现有的拟胆碱驱虫药不敏感。我们发现EAT-18是一种新型的辅助亚基蛋白，对于受体的功能表达至关重要。EAT-18与成熟受体直接相互作用，和不同的同系物会改变药理特性。因此，我们不仅描述了一种新型的潜在药物靶标，而且还描​​述了一种新型的nAChRs专性辅助蛋白。