One of the tenets of molecular biology is that dynamic transitions between three-dimensional structures determine the function of proteins. Therefore, it seems only natural that evolutionary analysis of proteins, presently based mainly on their primary sequence, needs to shift its focus toward their function as assessed by corresponding structural transitions. This can be facilitated by recent progress in cryogenic electron microscopy that provides atomic structures of multiple conformational states for proteins and protein assemblies isolated from evolutionarily related species. In this work, we study evolutionary conservation of multiprotein assembly function by using mechanical strain as a quantitative footprint of structural transitions. We adopt the formalism of finite strain theory, developed in condensed matter physics, and apply it, as a case study, to a classical multiprotein assembly, the ATP synthase. Protein strain analysis provides a precise characterization of rotation domains that agrees with the present biophysical knowledge. In addition, we obtain a strain distribution on the protein structure associated with functional transitions. By analyzing in detail the strain patterns of the chains responsible for ATP synthesis across distinct species, we show that they are evolutionarily conserved for the same functional transition. Such conservation is not revealed by displacement or rotation patterns. Furthermore, within each functional transition, we can identify conserved strain patterns for ATP synthases isolated from different organisms. The observed strain conservation across evolutionary distant species indicates that strain should be essential in future structure-based evolutionary studies of protein function.

中文翻译：

---

蛋白质结构功能转变中机械应变分布的进化守恒

分子生物学的原则之一是三维结构之间的动态转变决定蛋白质的功能。因此，目前主要基于其一级序列的蛋白质进化分析需要将其重点转向通过相应的结构转变评估的功能，这似乎是很自然的。低温电子显微镜的最新进展可以促进这一点，低温电子显微镜为从进化相关物种中分离出的蛋白质和蛋白质组装体提供了多种构象状态的原子结构。在这项工作中，我们通过使用机械应变作为结构转变的定量足迹来研究多蛋白组装功能的进化保守性。我们采用凝聚态物理学中发展起来的有限应变理论的形式，并将其作为案例研究应用于经典的多蛋白组装体，即 ATP 合酶。蛋白质应变分析提供了与当前生物物理学知识一致的旋转域的精确表征。此外，我们还获得了与功能转变相关的蛋白质结构的应变分布。通过详细分析不同物种中负责 ATP 合成的链的应变模式，我们表明它们在进化上对于相同的功能转变是保守的。这种守恒并不能通过位移或旋转模式来揭示。此外，在每个功能转变中，我们可以识别从不同生物体中分离出的 ATP 合酶的保守菌株模式。观察到的进化远缘物种的应变保守性表明，应变在未来基于结构的蛋白质功能进化研究中应该是必不可少的。