Retraction notice to: Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gβ1γ2.
Retraction notice to: Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gβ1γ2.
复制标题
撤回通知：甲状旁腺激素受体 C 末端与 G 蛋白二聚体 Gβ1γ2 结合的结构。
DOI：
10.1016/j.str.2011.07.010
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发表时间：
2011
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Gbg二聚体在异源三聚体G蛋白信号传导中的关键作用是通过细胞表面G蛋白偶联受体促进Ga亚基的接合和活化。然而，受体和Gbg二聚体之间的连接的高分辨率结构信息以前还没有。在这里，我们描述的结构决定因素Gb 1G 2在复杂的甲状旁腺激素受体-1（PTH 1 R）的C-末端区域，通过X-射线晶体学获得。该结构揭示了PTH 1 R内的几个关键残基仅接触位于Gb环形结构的WD 1-和WD 7-重复片段的外边缘内的Gb残基。这些区域包括一个预测的膜面向区域的Gb被认为是取向的方式，是跨膜受体。Gb 1上关键受体接触残基的突变导致受体/异源三聚体偶联功能的选择性丧失，同时保留效应磷脂酶-C B的Gb 1g 2激活。
A critical role of the Gbg dimer in heterotrimeric G-protein signaling is to facilitate the engagement and activation of the Ga subunit by cell-surface G-protein-coupled receptors. However, high-resolution structural information of the connectivity between receptor and the Gbg dimer has not previously been available. Here, we describe the structural determinants of Gb1g2 in complex with a C-terminal region of the parathyroid hormone receptor-1 (PTH1R) as obtained by X-ray crystallography. The structure reveals that several critical residues within PTH1R contact only Gb residues located within the outer edge of WD1-and WD7-repeat segments of the Gb toroid structure. These regions encompass a predicted membrane-facing region of Gb thought to be oriented in a fashion that is accessible to the membrane-spanning receptor. Mutation of key receptor contact residues on Gb1 leads to a selective loss of function in receptor/heterotrimer coupling while preserving Gb1g2 activation of the effector phospholipase-C b.