Kersten S, Pan L, Chambon P, Gronemeyer H, Noy N
Cornell University, Division of Nutritional Sciences, Ithaca, New York 14853-6301, USA.
Biochemistry. 1995 Oct 24;34(42):13717-21. doi: 10.1021/bi00042a001.
Many of the effects of retinoids on cells are mediated by the transcription factors known as retinoid nuclear receptors, but the mechanisms by which retinoids regulate the activity of the receptors are not known. It was previously shown that the retinoid X receptor (RXR) forms tetramers with a high affinity. In the present work it is demonstrated that binding of 9-cis-retinoic acid to RXR leads to rapid dissociation of receptor tetramers. In addition, fluorescence anisotropy studies indicate that ligand-binding results in a significant conformational change such that holo-RXR is more compactly folded as compared to the apo-protein. These findings suggest that the initial event in signaling by 9-cis-retinoic acid is a change in the oligomeric state of RXR. The data also imply that tetramer formation is a regulatory feature of the pathway by which RXR mediates the effects of retinoids on gene transcription.
维甲酸对细胞的许多作用是由被称为维甲酸核受体的转录因子介导的，但维甲酸调节这些受体活性的机制尚不清楚。此前已表明，维甲酸X受体（RXR）以高亲和力形成四聚体。在本研究中，证明了9-顺式维甲酸与RXR的结合导致受体四聚体迅速解离。此外，荧光各向异性研究表明，配体结合会导致显著的构象变化，使得与脱辅基蛋白相比，全反式RXR折叠得更紧密。这些发现表明，9-顺式维甲酸信号传导的初始事件是RXR寡聚状态的改变。数据还暗示，四聚体形成是RXR介导维甲酸对基因转录作用的途径的一个调节特征。
