Dynamic Transmission of Protein Allostery without Structural Change: Spatial Pathways or Global Modes?

Dynamic Transmission of Protein Allostery without Structural Change: Spatial Pathways or Global Modes?
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DOI:
10.1016/j.bpj.2015.08.009
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发表时间:
2015-09-15
影响因子:
3.4
通讯作者:
Rodgers, Thomas L.
Rodgers, Thomas L.
中科院分区:
生物学3区
文献类型:
--
作者:
McLeish, Tom C. B.;Cann, Martin J.;Rodgers, Thomas L.

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我们从变构途径的角度考察了涉及结构变化的变构信号机制与不涉及结构变化的变构信号机制之间的对比。特别是,我们详细地处理了涨落变构的情况,弹性简正模的热涨落的幅度调制传递了变构信号,并解决了变构路径在这种情况下意味着什么的问题。我们发现,热弹性固体的微扰理论和非微扰方法(通过将超粗晶弹性转化为内弯曲模式)在它们的关联路径结构中具有相反的特征。我们举例说明了对谷氨酸棒杆菌GlxR先前结果的分析的影响,谷氨酸棒杆菌是变构同源二聚体的CRP/FNR转录家族的一个例子。我们发现,在这个蛋白质中,相关的路径和不相连的相关运动位置的可见性表明,局部弹性拉伸和弯曲机制被用来创建和控制变构协作性。
We examine the contrast between mechanisms for allosteric signaling that involve structural change, and those that do not, from the perspective of allosteric pathways. In particular we treat in detail the case of fluctuation-allostery by which amplitude modulation of the thermal fluctuations of the elastic normal modes conveys the allosteric signal, and address the question of what an allosteric pathway means in this case. We find that a perturbation theory of thermal elastic solids and non-perturbative approach (by super-coarse-graining elasticity into internal bending modes) have opposite signatures in their structure of correlated pathways. We illustrate the effect from analysis of previous results from GlxR of Corynebacterium glutamicum, an example of the CRP/FNR transcription family of allosteric homodimers. We find that the visibility of both correlated pathways and disconnected sites of correlated motion in this protein suggests that mechanisms of local elastic stretch and bend are recruited for the purpose of creating and controlling allosteric cooperativity.