Network models reveal stability and structural rearrangement of signal recognition particle

The signal recognition particle (SRP) and its receptors (SR) mediate the cotranslational targeting of the membrane and secretory proteins in all cells. In Escherichia coli, SRP is composed of the Ffh protein and the 4.5S SRP RNA. Ffh is a multidomain protein comprising a methionine-rich (M) domain, a helical N domain, and a Ras-like guanine triphosphatase (GTPase) (G) domain. The N and G domains are commonly referred to as one structural unit, the NG domain. In this article, the complex structure of SRP and SR is investigated with the Gaussian network model (GNM) and anisotropic network model (ANM). GNM provides the information of structure stability. It is found that the intermolecular interactions between SRP and SR can obviously decrease the fluctuation of NG domains. Nevertheless, the large structural rearrangement will take place during the cotranslational protein targeting cycle. Hence, the moving directions of fluctuation regions are further ascertained by using cross-correlation analysis and the ANM. The NG domain of Ffh undergoes a clockwise rotation around the GM linker and the M domain of Ffh shows an opposite direction to the NG domain. These functional movements will facilitate the SRP structure to transform into the free form and the sequence-bound form. These simple coarse-grained analyses can be used as a general and quick method for the mechanism studies of protein assembly and supramolecular systems.

信号识别颗粒（signal recognition particle，SRP）及其受体（SR）介导所有细胞中膜蛋白与分泌蛋白的共翻译靶向过程。在大肠杆菌中，SRP由Ffh蛋白与4.5S SRP核糖核酸（RNA）组成。Ffh是一种多结构域蛋白，包含富含甲硫氨酸的M结构域、螺旋N结构域以及类Ras鸟苷三磷酸酶（GTPase）G结构域。通常将N结构域与G结构域合称为一个结构单元，即NG结构域。
本文采用高斯网络模型（Gaussian network model，GNM）与各向异性网络模型（anisotropic network model，ANM）对SRP与SR的复合物结构开展研究。GNM可提供结构稳定性相关信息。研究发现，SRP与SR之间的分子间相互作用可显著降低NG结构域的波动幅度。然而，在共翻译蛋白靶向循环过程中会发生大规模的结构重排。因此，本文进一步通过互相关分析与ANM确定了波动区域的运动方向：Ffh的NG结构域围绕GM连接区发生顺时针旋转，而Ffh的M结构域运动方向与NG结构域相反。这类功能性运动可促使SRP结构向游离形式与序列结合形式转变。上述简易粗粒度分析可作为一种通用且快速的方法，用于蛋白组装与超分子系统的作用机制研究。