Photoaffinity labeling of the sigma-1 receptor with N-[3-(4-nitrophenyl)propyl]-N-dodecylamine: evidence of receptor dimers.
Photoaffinity labeling of the sigma-1 receptor with N-[3-(4-nitrophenyl)propyl]-N-dodecylamine: evidence of receptor dimers.
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DOI：
10.1021/bi301517u
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发表时间：
2013-02-05
期刊：
影响因子：
2.9
通讯作者：
Ruoho AE
中科院分区：
文献类型：
--
作者：
Chu UB;Ramachandran S;Hajipour AR;Ruoho AE
σ-1受体是一种配体调节的ER常驻伴侣，参与维持细胞内稳态。σ-1受体与各种ER和/或质膜离子通道的偶联与其调节响应于σ-1受体配体产生的运动活性和细胞增殖的能力相关。许多内源性小分子与σ-1受体结合，并已被证明可调节其活性;这些小分子包括孕酮、N，N-二甲基色胺、D-β-鞘氨醇和/或其他内源性脂质。我们以前报道了长链N-烷基胺衍生物的合成和N-烷基胺的链长和在sigma-1受体的亲和力之间的结构-活性关系的表征。在这里，我们目前的数据表明，光掺入这些N-烷基胺衍生物，4-NPPC 12，σ-1受体之一。MALDI-TOF-TOF和串联质谱显示4-NPPC 12光插入在sigma-1受体的衍生群体的组氨酸154处。有趣的是，4-NPPC 12的光依赖性光插入导致通过SDS聚丙烯酰胺凝胶电泳评估的仅50%的衍生化受体分子的电泳迁移率增强。提出的4-NPPC 12的结合和反应性引发了σ-1受体的配体结合模型，其可能涉及受体二聚体和/或寡聚体。
The sigma-1 receptor is a ligand-regulated ER resident chaperone involved in the maintenance of cellular homeostasis. Coupling of the sigma-1 receptor with various ER and/or plasma membrane ion channels is associated with its ability to regulate the locomotor activity and cellular proliferation produced in response to sigma-1 receptor ligands. A number of endogenous small molecules bind to the sigma-1 receptor and have been shown to regulate its activity; these include progesterone, N,N-dimethyltryptamine, D-erythro-sphingosine, and/or other endogenous lipids. We previously reported the synthesis of long chain N-alkylamine derivatives and the characterization of the structural-activity relationship between chain length of N-alkylamine and affinities at the sigma-1 receptor. Here, we present data demonstrating the photo-incorporation of one of these N-alkylamine derivatives, 4-NPPC12, to the sigma-1 receptor. MALDI-TOF-TOF and tandem mass spectrometry showed that 4-NPPC12 photo-inserted at histidine 154 of the derivatized population of the sigma-1 receptor. Interestingly, light dependent photo-insertion of 4-NPPC12 resulted in an enhanced electrophoretic mobility of only 50% of the derivatized receptor molecules as assessed by SDS polyacrylamide gel electrophoresis. The proposed binding and reactivity of 4-NPPC12 evokes a ligand binding model for the sigma-1 receptor that likely involves a receptor dimer and/or oligomer.
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DOI：
10.1126/science.1166127
发表时间：
2009-02-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fontanilla D;Johannessen M;Hajipour AR;Cozzi NV;Jackson MB;Ruoho AE
通讯作者：
Ruoho AE
DOI：
10.1006/bbrc.1996.1842
发表时间：
1996-12-13
影响因子：
3.1
作者：
Kekuda, R;Prasad, PD;Ganapathy, V
通讯作者：
Ganapathy, V
影响因子：
3.6
作者：
Hayashi, Teruo;Fujimoto, Michiko
通讯作者：
Fujimoto, Michiko
影响因子：
1.6
作者：
Ramachandran, Subramaniam;Lu, Hongliang;Ruoho, Arnold E.
通讯作者：
Ruoho, Arnold E.
DOI：
10.1073/pnas.89.4.1393
发表时间：
1992-02-15
影响因子：
11.1
作者：
KAHOUN, JR;RUOHO, AE
通讯作者：
RUOHO, AE