论文标题
综合动态结构生物学揭示了对大GTPase的低聚至关重要
Integrative dynamic structural biology unveils conformers essential for the oligomerization of a large GTPase
论文作者
论文摘要
鸟苷酸盐结合蛋白（GBP）是可溶性动力蛋白样蛋白，具有结构化结构域，其经历了GTP控制的寡聚的构象转变，以使其功能作为哺乳动物细胞的先天免疫系统的一部分 - 通过破坏膜膜的胶体内寄生虫的象征。该过程的结构基础和机制尚不清楚。因此，我们将中子自旋回波，X射线散射，荧光和EPR光谱应用于人类GBP1（HGBP1）的整合动态结构生物学技术。我们绘制了HGBP1的基本动力学，从纳米秒到毫秒到毫秒的动态。我们发现$ $ $ $ s-Legime中C-末端效应域无关GTP的灵活性，结构表征构象体至关重要，即HGBP1可以像袖珍刀那样打开以进行寡聚。这揭示了固有的柔韧性，这是GTP触发的GTPase域和组装依赖性的GTP-Hydrolsyss的关联，作为HGBP1的功能设计原理，控制其在极性组装中的可逆寡聚化和后续冷凝物的形成。
Guanylate binding proteins (GBPs) are soluble dynamin-like proteins with structured domains that undergo a conformational transition for GTP-controlled oligomerization to exert their function as part of the innate immune system of mammalian cells - attacking intra-cellular parasites by disrupting their membranes. The structural basis and mechanism of this process is unknown. Therefore, we apply neutron spin echo, X-ray scattering, fluorescence, and EPR spectroscopy as techniques for integrative dynamic structural biology to human GBP1 (hGBP1). We mapped hGBP1's essential dynamics from nanoseconds to milliseconds by motional spectra of sub-domains. We find a GTP-independent flexibility of the C-terminal effector domain in the $μ$s-regime and structurally characterize conformers being essential that hGBP1 can open like a pocketknife for oligomerization. This unveils the intrinsic flexibility, a GTP-triggered association of the GTPase-domains and assembly-dependent GTP-hydrolysis as functional design principles of hGBP1 that control its reversible oligomerization in polar assemblies and the subsequent formation of condensates.
