Receptor and Subunit Specific Interactions of RIC-3 with Nicotinic Acetylcholine Receptors
Receptor and Subunit Specific Interactions of RIC-3 with Nicotinic Acetylcholine Receptors
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DOI：
10.1021/bi901234a
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发表时间：
2009-12-29
期刊：
影响因子：
2.9
通讯作者：
Treinin, Millet
中科院分区：
文献类型：
--
作者：
Ben-Ami, Hagit Cohen;Biala, Yoav;Treinin, Millet
RIC-3属于影响烟碱乙酰胆碱受体（nAChR）成熟的保守蛋白质家族。RIC-3同源物显示出不同地影响不同的nAChR。在这里，我们发现与RIC-3的共表达增加了DEG-3的表面表达水平，同时略微降低了DES-2的表面表达水平，DES-2是DEG-3/DES-2 nAChR的两个亚基。这些不同的作用是对先前证实的RIC-3（一种内质网驻留蛋白）作用的可能解释，该受体具有油特性。为了了解RIC-3如何与不同的nAChR亚基相互作用，我们鉴定并表征了能够实现这种相互作用的结构域和残基。该分析表明，第二RIC-3跨膜结构域中的保守残基是其与两种不同的秀丽隐杆线虫nAChR（DEG-3/DES-2和ACR-16）相互作用所必需的。然而，这些保守的残基并不单独起作用;相反，我们发现额外的结构域也使RIC-3与这些受体相互作用。有趣的是，这些残基或介导RIC-3与nACh Rs相互作用的其他结构域的相对重要性对于两种不同的受体不同。RIC-3被预测为所有内在无序的蛋白质，与不同受体和受体亚基相互作用的方式差异表明它可能采用不同的构象来实现这些相互作用。这种差异可以解释RIC-3对受体特性的影响以及其对不同受体的影响的差异。
RIC-3 belongs to a conserved family of proteins influencing maturation of nicotinic acetylcholine receptors (nAChRs). RIC-3 homologues were shown to differently affect different nAChRs. Here we show that coexpression with RIC-3 increases the level Of Surface expression of DEG-3 while slightly reducing the level of surface expression of DES-2, both subunits of the DEG-3/DES-2 nAChRs. Those different effects are a likely explanation for the previously demonstrated effects of RIC-3, an endoplasmic reticulum resident protein, oil properties of this receptor. TO understand how RIC-3 interacts with different nAChR Subunits, we identified and characterized domains and residues enabling this interaction. This analysis shows that conserved residues in the second RIC-3 transmembrane domain are needed for its interactions with two different Caenorhabditis elegans nAChRs, DEG-3/DES-2 and ACR-16. These conserved residues do not, however, function alone; rather, we show that additional domains also enable RIC-3's interactions with these receptors. Interestingly, the relative importance of these residues or of other domains mediating interactions of RIC-3 with nACh Rs differs for the two different receptors. Differences in the way that RIC-3, predicted to be all intrinsically disordered protein, interacts with different receptors and receptor subunits suggest that it may adopt different conformations to enable these interactions. Such differences may explain both the effects of RIC-3 on receptor properties and the differences in its effects on different receptors.