Structure and signaling mechanism of Per-ARNT-Sim domains.

Structure and signaling mechanism of Per-ARNT-Sim domains.
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DOI:
10.1016/j.str.2009.08.011
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发表时间:
2009-10-14
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Moffat K
Moffat K
中科院分区:
其他
文献类型:
--
作者:
Möglich A;Ayers RA;Moffat K

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Per-Arnt-Sim(PAS)结构域是信号转导蛋白中分布广泛、用途广泛的传感器和相互作用模块。PAS传感器可以检测多种化学和物理刺激,并调节不同功能效应域的活动。与这种化学、物理和功能的多样性相反,PAS结构域的核心结构是广泛保守的,由一个五链的反平行β-折叠和几个α-螺旋组成。信号起源于保守的核心内,并产生结构和动态变化,主要是在β-Sheet内,它们通过核心N-末端或C-末端的两亲性α-螺旋和盘状线圈连接子传播到共价连接的效应结构域。效应域通常是二聚体的;它们的活性似乎在很大程度上受到信号依赖的四级结构和动力学变化的调节。PAS和其他信号域的信号机制具有共同的特征,这些共同之处可以被用来进行基于结构的人工光传感器和化学传感器的设计。
Per-ARNT-Sim (PAS) domains serve as widely-distributed, versatile, sensor and interaction modules in signal transduction proteins. PAS sensors detect a wide range of chemical and physical stimuli and regulate the activity of functionally diverse effector domains. In contrast to this chemical, physical and functional diversity, the structure of the core of PAS domains is broadly conserved and comprises a five-stranded antiparallel β-sheet and several α-helices. Signals originate within the conserved core and generate structural and dynamic changes predominantly within the β-sheet, from which they propagate via amphipathic α-helical and coiled-coil linkers at the N- or C-termini of the core to the covalently-attached effector domain. Effector domains are typically dimeric; their activity appears to be largely regulated by signal-dependent changes in quaternary structure and dynamics. The signaling mechanisms of PAS and other signaling domains share common features, and these commonalities can be exploited to enable structure-based design of artificial photo- and chemosensors.
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