由于蛋白质交换失调而导致低氧反应的过敏终止
Rebecca B Berlow1, H Jane Dyson1, Peter E Wright1
1Department of Integrative Structural and Computational Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|March 9, 2017
概括
通过从TAZ1中取代HIF-1α,CITED2蛋白迅速降低细胞低氧反应. 这通过一种短暂的复合体发生,促进HIF-1α的释放并激活敏感的负反循环.
科学领域:
- 分子生物学
- 细胞信号传输
- 蛋白与蛋白的相互作用
背景情况:
- 细胞对低氧的反应对于生存和适应至关重要.
- 低氧诱导因子1α (HIF-1α) 通过CBP/ p300的TAZ1域调节适应基因.
- 通过竞争TAZ1结合,CITED2充当负反调节器.
研究的目的:
- 阐明CITED2从TAZ1中取代HIF-1α的分子机制.
- 了解CITED2如何激活控制低氧反应的负反回路.
主要方法:
- 研究了CITED2,HIF-1α和TAZ1之间的相互作用.
- 在TAZ1结合和位移中描述了保留LP(Q/E) L基因的作用.
- 利用对内在无序蛋白质的研究来解释调节开关.
主要成果:
- 人类CITED2通过与TAZ1形成一个短暂的三元复合物来取代HIF-1α.
- CITED2的LPEL图案在同一结合点上竞争,导致TAZ1的形状变化.
- 这种形状变化会使HIF-1α解离增强,从而激活快速的负反循环.
结论:
- CITED2激活了一个高度响应的负反电路,以减弱低氧反应.
- 过敏性调节依赖于内在无序的蛋白质的独特特性.
- 这种机制可能代表了快速环境信号响应的常见细胞策略.
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