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Commentary on “Novel Interaction of the Dopamine D2 Receptor and the Ca2+Binding Protein S100B: Role in D2 Receptor Function”
Molecular Pharmacology ( IF 3.6 ) Pub Date : 2021-08-01 , DOI: 10.1124/molpharm.121.000284
Hun-Joo Lee 1 , Dayana Rodriguez-Contreras 1 , Kim A Neve 2
Affiliation  

We previously proposed that the dopamine D2 receptor–interacting protein S100B binds to a putative S100B-binding motif at residues R233–L240 toward the N terminus of the third intracellular loop. We used in vitro pull-down assays with FLAG-tagged fragments of the rat dopamine D2 receptor third intracellular loop (D2-IC3) and in vitro-synthesized S100B to evaluate this hypothesis. Our results indicate that the putative S100B-binding motif is neither necessary nor sufficient for strong binding of S100B to D2-IC3. Instead, two residues at the junction of the fifth membrane-spanning domain and the cytoplasmic extension of that α-helical domain, K211-I212, are required for robust, calcium-sensitive binding of S100B. This is also the approximate location of previously identified determinants for the binding of arrestin and calmodulin. A D2 receptor mutation converting I212 to phenylalanine has been described in patients with a hyperkinetic movement disorder.

中文翻译:

评论“多巴胺 D2 受体与 Ca2+结合蛋白 S100B 的新型相互作用:在 D2 受体功能中的作用”

我们之前提出多巴胺 D2 受体相互作用蛋白 S100B 与推定的 S100B 结合基序结合,位于第三个细胞内环的 N 末端残基 R233-L240。我们使用带有 FLAG 标记的大鼠多巴胺 D2 受体第三胞内环 (D2-IC3) 片段和体外合成的 S100B 的体外下拉分析来评估这一假设。我们的结果表明,假定的 S100B 结合基序对于 S100B 与 D2-IC3 的强结合既不必要也不充分。取而代之的是,在第五个跨膜结构域和该α的细胞质延伸连接处的两个残基-螺旋结构域 K211-I212 是 S100B 的稳健、钙敏感性结合所必需的。这也是先前确定的抑制蛋白和钙调蛋白结合的决定因素的大致位置。已在多动症患者中描述了将 I212 转化为苯丙氨酸的 D2 受体突变。
更新日期:2021-08-31
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