Abstract:
The Sigma-1 Receptor (S1R) is a small, ligand-regulated integral membrane protein involved in cell homeostasis and the cellular stress response. The receptor has a multitude of protein and small molecule interaction partners with therapeutic potential. Newly reported structures of the human S1R in ligand-bound states provides essential insights into small molecule binding in the context of the overall protein structure. The structure also raises many interesting questions and provides an excellent starting point for understanding the molecular tricks employed by this small membrane receptor to modulate a large number of signaling events. Here, we review insights from the structures of ligand-bound S1R in the context of previous biochemical studies and propose, from a structural viewpoint, a set of important future directions.
摘要:
Sigma-1受体(S1R)是一个小的,配体调节的整合膜蛋白参与细胞稳态和细胞应激反应。该受体具有多种具有治疗潜力的蛋白质和小分子相互作用伙伴。新报道的处于配体结合状态的人S1R的结构提供了在整体蛋白质结构的背景下对小分子结合的基本见解。该结构还提出了许多有趣的问题,并为理解这种小膜受体用来调节大量信号传导事件的分子技巧提供了极好的起点。这里,我们在先前的生化研究的背景下回顾了配体结合的S1R结构的见解,并提出,从结构的角度来看,一系列重要的未来方向。