ADP-ribosylation factor 1 (Arf1) interacts with multiple cellular partners and membranes to regulate intracellular traffic, organelle structure and actin dynamics. Defining the dynamic conformational landscape of Arf1 in its active form, when bound to the membrane, is of high functional relevance and key to understanding how Arf1 can alter diverse cellular processes. Through concerted application of nuclear magnetic resonance (NMR), neutron reflectometry (NR) and molecular dynamics (MD) simulations, we show that, while Arf1 is anchored to the membrane through its N-terminal myristoylated amphipathic helix, the G domain explores a large conformational space, existing in a dynamic equilibrium between membrane-associated and membrane-distal conformations. These configurational dynamics expose different interfaces for interaction with effectors. Interaction with the Pleckstrin homology domain of ASAP1, an Arf-GTPase activating protein (ArfGAP), restricts motions of the G domain to lock it in what seems to be a conformation exposing functionally relevant regions.

ADP-核糖基化因子 1 (Arf1) 与多个细胞伴侣和细胞膜相互作用，调节细胞内交通、细胞器结构和肌动蛋白动力学。定义 Arf1 活性形式与膜结合时的动态构象景观具有高度的功能相关性，也是理解 Arf1 如何改变多种细胞过程的关键。通过核磁共振 (NMR)、中子反射计 (NR) 和分子动力学 (MD) 模拟的协同应用，我们表明，虽然 Arf1 通过其 N 端肉豆蔻酰化两亲螺旋锚定在膜上，但 G 结构域探索了大的构象空间，存在于膜相关构象和膜远端构象之间的动态平衡。这些配置动态暴露了与效应器交互的不同接口。与 ASAP1（一种 Arf-GTP 酶激活蛋白 (ArfGAP)）的 Pleckstrin 同源结构域相互作用，限制 G 结构域的运动，将其锁定在似乎暴露功能相关区域的构象中。