...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Loop-loop interactions regulate KaiA-stimulated KaiC phosphorylation in the cyanobacterial KaiABC circadian clock
【24h】

Loop-loop interactions regulate KaiA-stimulated KaiC phosphorylation in the cyanobacterial KaiABC circadian clock

机译：环-环相互作用调节蓝细菌KaiABC昼夜节律中的KaiA刺激的KaiC磷酸化。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The Synechococcus elongatus KaiA, KaiB, and KaiC proteins in the presence of ATP generate a post-translational oscillator that runs in a temperature-compensated manner with a period of 24 h. KaiA dimer stimulates phosphorylation of KaiC hexamer at two sites per subunit, T432 and S431, and KaiB dimers antagonize KaiA action and induce KaiC subunit exchange. Neither the mechanism of KaiA-stimulated KaiC phosphorylation nor that of KaiB-mediated KaiC dephosphorylation is understood in detail at present. We demonstrate here that the A422V KaiC mutant sheds light on the former mechanism. It was previously reported that A422V is less sensitive to dark pulse-induced phase resetting and has a reduced amplitude of the KaiC phosphorylation rhythm in vivo. A422 maps to a loop (422-loop) that continues toward the phosphorylation sites. By pulling on the C-terminal peptide of KaiC (A-loop), KaiA removes restraints from the adjacent 422-loop whose increased flexibility indirectly promotes kinase activity. We found in the crystal structure that A422V KaiC lacks phosphorylation at S431 and exhibits a subtle, local conformational change relative to wild-type KaiC. Molecular dynamics simulations indicate higher mobility of the 422-loop in the absence of the A-loop and mobility differences in other areas associated with phosphorylation activity between wild-type and mutant KaiCs. The A-loop-422-loop relay that informs KaiC phosphorylation sites of KaiA dimer binding propagates to loops from neighboring KaiC subunits, thus providing support for a concerted allosteric mechanism of phosphorylation.
机译：在ATP的存在下，伸长的Synechococcus elongatus KaiA，KaiB和KaiC蛋白产生翻译后振荡器，该振荡器以温度补偿的方式运行，持续24小时。 KaiA二聚体在每个亚基T432和S431的两个位点刺激KaiC六聚体的磷酸化，而KaiB二聚体拮抗KaiA的作用并诱导KaiC亚基交换。目前尚不了解KaiA刺激的KaiC磷酸化的机制或KaiB介导的KaiC脱磷酸化的机制。我们在这里证明A422V KaiC突变体阐明了前一种机制。先前已有报道，A422V对暗脉冲诱导的相位重置较不敏感，并且体内的KaiC磷酸化节律幅度降低。 A422映射到一个继续朝着磷酸化位点的环（422环）。通过拉动KaiC的C端肽（A环），KaiA从相邻的422环中消除了约束，其增加的柔韧性间接促进了激酶活性。我们在晶体结构中发现，A422V KaiC在S431处缺乏磷酸化，相对于野生型KaiC表现出细微的局部构象变化。分子动力学模拟表明，在没有A环的情况下422环具有更高的迁移率，而其他区域的迁移率差异与野生型和突变型KaiC之间的磷酸化活性有关。通知KaiA二聚体结合的KaiC磷酸化位点的A环422环继电器从邻近的KaiC亚基传播到环，从而为磷酸化的协同变构机制提供了支持。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号