Modulation of GDP release from transducin by the conserved Glu(134)-Arg(135) sequence in rhodopsin

Modulation of GDP release from transducin by the conserved Glu(134)-Arg(135) sequence in rhodopsin
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DOI:
10.1074/jbc.271.41.25406
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发表时间:
1996-10-11
影响因子:
4.8
通讯作者:
Karnik, SS
Karnik, SS
中科院分区:
生物学2区
文献类型:
--
作者:
Acharya, S;Karnik, SS

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一个七跨膜螺旋受体超家族催化异源三聚体鸟嘌呤核苷酸结合蛋白释放GDP光感受器视紫红质是激活视网膜G蛋白转导素(G(t))的超家族的原型成员,视紫红质的胞质结构域结合并激活G(t),但刺激G(t)释放GDP的残基至今尚未被鉴定,我们在这里表明,影响高度保守的Glu(134)-Arg(135)的几种不同突变的异常信号转导表型,G(t)激活级联反应中GDP释放步骤的改变产生电荷对,我们提出Glu(134)和Arg(135)构成直接提供来自视紫红质的信号以激活G(t)的GDP释放的位点,由于Glu/Asp-Arg序列发生在拓扑结构上相同的位置,在大多数的七跨膜螺旋受体,我们建议,这些残基构成一个开关的信号传递。
A superfamily of seven-transmembrane helix receptors catalyzes GDP release from heterotrimeric guanine nucleotide-binding proteins (G proteins) to initiate the intracellular signaling cascade, The photoreceptor rhodopsin is a prototypical member of the superfamily that activates the retinal G protein transducin (G(t)), The cytoplasmic domain of rhodopsin binds and activates G(t), but residues that stimulate GDP release from G(t) have not been identified until now, We show here that the abnormal signal transduction phenotypes of several different mutations affecting the highly conserved Glu(134)-Arg(135) charge pair result from alteration of the GDP release step in the G(t) activation cascade, We propose that Glu(134) and Arg(135) constitute the site that directly provides the signal from rhodopsin to activate GDP release from G(t), Because the Glu/Asp-Arg sequence occurs at a topologically identical location in most of the seven-transmembrane helix receptors, we propose that these residues constitute a switch for signal transfer.