Structural insights into a circadian oscillator.

Structural insights into a circadian oscillator.
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对昼夜节律振荡器的结构见解。

DOI:
10.1126/science.1150451
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发表时间:
2008-10-31
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Stewart PL
Stewart PL
中科院分区:
其他
文献类型:
--
作者:
Johnson CH;Egli M;Stewart PL

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蓝藻的内源性昼夜节律系统对包括全球基因表达在内的细胞过程施加普遍控制。事实上,整个染色体每天都在经历拓扑变化和压缩的循环。仅用三种蓝藻蛋白,KaiA, KaiB和KaiC,就可以在体外重建昼夜节律振荡器的生化机制。这些蛋白相互作用促进构象变化和磷酸化事件,从而决定体外振荡的阶段。这些蛋白质的高分辨率结构表明,KaiABC振荡器存在一种单向摆动机制。这种翻译后振荡器可能与转录和翻译反馈回路相互作用,在体内产生紧急的昼夜节律行为。结构、生物物理和生物化学方法的结合揭示了生物计时的分子机制。
An endogenous circadian system in cyanobacteria exerts pervasive control over cellular processes including global gene expression. Indeed, the entire chromosome undergoes daily cycles of topological changes and compaction. The biochemical machinery underlying a circadian oscillator can be reconstituted in vitro with just three cyanobacterial proteins, KaiA, KaiB, and KaiC. These proteins interact to promote conformational changes and phosphorylation events that determine the phase of the in vitro oscillation. The high-resolution structures of these proteins suggest a racheting mechanism by which the KaiABC oscillator ticks unidirectionally. This post-translational oscillator may interact with transcriptional and translational feedback loops to generate the emergent circadian behavior in vivo. The conjunction of structural, biophysical, and biochemical approaches to this system reveals molecular mechanisms of biological timekeeping.
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