Sodium- and chloride-dependent transporters in brain, kidney, and gut: lessons from complementary DNA cloning and structure-function studies.
Sodium- and chloride-dependent transporters in brain, kidney, and gut: lessons from complementary DNA cloning and structure-function studies.
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脑、肾和肠道中钠和氯依赖性转运蛋白：互补 DNA 克隆和结构功能研究的教训。
DOI：
10.1097/00041552-199309000-00008
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发表时间：
1993
影响因子：
3.2
通讯作者：
Uhl,GR
中科院分区：
文献类型：
--
作者：
Surratt,CK;Wang,JB;Yuhasz,S;Amzel,M;Kwon,HM;Handler,JS;Uhl,GR
Na+-和Cl-依赖的12个跨膜结构域转运蛋白家族现在包括脑中神经递质分子和神经元组织（包括肾上腺、肾和肠）中重要物质的转运蛋白。转运的底物包括单胺和氨基酸神经递质和非渗透压物质。一个共同的蛋白质拓扑结构的预测和功能细胞内的N-和C-末端拥有磷酸化位点和至少一个大的膜外环与N-连接的糖基化。使用大鼠多巴胺转运蛋白作为模板，分子建模的推定跨膜结构域加上氨基酸序列保守性分析表明，潜在的参与底物和/或离子识别的氨基酸残基。定点突变靶向这些残基将有助于澄清底物和离子结合位点，并应促进合理设计治疗抑郁症，运动障碍和药物滥用。
The family of Na+-and Cl-dependent, 12 transmembrane domain transporter proteins now includes transporters for neuretransmitter molecules in the brain and for substances important in extraneuronal tissues, including adrenal, kidney, and gut. Transported substrates include monoamine and amino acid neuretransmitters and nonper-turbing osmolytes. A common protein topology is predicted and features intracellular N-and C-termini possessing phosphorylation sites and at least one large extramembranous loop with N-linked glycosylation. Using the rat dopamine transporter as a template, molecular modeling of putative transmembrane domains coupled with amino acid sequence conservation analysis indicates amino acid residues potentially involved in substrate and/or ion recognition. Targeting such residues with site-directed mutagenesis will help clarify substrate and ion binding sites and should facilitate rational design of therapeutics to combat depression, locomotor disorders, and substance abuse.