Allosteric conformational ensembles have unlimited capacity for integrating information.
Allosteric conformational ensembles have unlimited capacity for integrating information.
复制标题
DOI：
10.7554/elife.65498
复制
发表时间：
2021-06-09
期刊：
影响因子：
7.7
通讯作者：
Gunawardena J
中科院分区：
文献类型：
--
作者：
Biddle JW;Martinez-Corral R;Wong F;Gunawardena J
大分子实体整合结合信息是细胞功能的基础。最近的工作表明，这种整合不能解释成对的合作，其中绑定调制绑定在另一个网站。高阶协同性（HOCs），其中结合是集体调制的多个其他结合事件，似乎是必要的，但一直缺乏适当的机制。我们在这里表明，HOCs通过变构产生，其中有效的协同性间接出现从动态互换构象的合奏。构象系综在许多细胞过程中发挥重要作用，但其整合能力仍然知之甚少。我们表明，足够复杂的合奏可以实现任何形式的信息集成，而无需能源消耗，包括所有模式的HOCs。我们的研究结果提供了一个严格的生物物理基础分析结合信息通过变构的整合。我们讨论了真核基因调控的影响，复杂的构象动力学伴随着广泛的信息整合。
Integration of binding information by macromolecular entities is fundamental to cellular functionality. Recent work has shown that such integration cannot be explained by pairwise cooperativities, in which binding is modulated by binding at another site. Higher-order cooperativities (HOCs), in which binding is collectively modulated by multiple other binding events, appear to be necessary but an appropriate mechanism has been lacking. We show here that HOCs arise through allostery, in which effective cooperativity emerges indirectly from an ensemble of dynamically interchanging conformations. Conformational ensembles play important roles in many cellular processes but their integrative capabilities remain poorly understood. We show that sufficiently complex ensembles can implement any form of information integration achievable without energy expenditure, including all patterns of HOCs. Our results provide a rigorous biophysical foundation for analysing the integration of binding information through allostery. We discuss the implications for eukaryotic gene regulation, where complex conformational dynamics accompanies widespread information integration.